An experimentally derived confidence score for binary protein-protein interactions (2009)
Braun, Pascal, Tasan, Murat, Dreze, Matija, Barrios-Rodiles, Miriam, Lemmens, Irma, Yu, Haiyuan, ...
Information on protein-protein interactions is of central importance for many areas of biomedical research. At present no method exists to systematically and experimentally assess the quality of...
Bmc Bioinformatics, Ian Donaldson, Joel Martin, Berry De Bruijn, Cheryl Wolting, Vicki Lay, ...
Research article PreBIND and Textomy – mining the biomedical literature for protein-protein interactions using a support vector machine
Colwill, Karen, Wells, Clark D, Elder, Kelly, Goudreault, Marilyn, Hersi, Kadija, Kulkarni, Sarang, ...
Abstract Background Recombinational systems have been developed to rapidly shuttle Open Reading Frames (ORFs) into multiple expression vectors in order to analyze the large number of cDNAs available...
Campellone, Kenneth Geno, Rankin, Susannah, Pawson, Tony, Kirschner, Marc W., Tipper, Donald J., Leong, John M.
Enteropathogenic Escherichia coli (EPEC) translocates effector proteins into mammalian cells to promote reorganization of the cytoskeleton into filamentous actin pedestals. One effector, Tir, is a...
Gruenheid, Samantha, Sekirov, Inna, Thomas, Nikhil A., Deng, Wanyin, O'Donnell, Paul, Goode, David, ...
Enterohaemorrhagic Escherichia coli (EHEC) O157:H7 uses a specialized protein translocation apparatus, the type III secretion system (TTSS), to deliver bacterial effector proteins into host cells....
Gruenheid, Samantha, Sekirov, Inna, Thomas, Nikhil A., Deng, Wanyin, O'Donnell, Paul, Goode, David, ...
Enterohaemorrhagic Escherichia coli (EHEC) O157:H7 uses a specialized protein translocation apparatus, the type III secretion system (TTSS), to deliver bacterial effector proteins into host cells....
Gruenheid, Samantha, Sekirov, Inna, Thomas, Nikhil A., Deng, Wanyin, O'Donnell, Paul, Goode, David, ...
Enterohaemorrhagic Escherichia coli (EHEC) O157:H7 uses a specialized protein translocation apparatus, the type III secretion system (TTSS), to deliver bacterial effector proteins into host cells....
Matthew J. Smith, Sarang Kulkarni, Tony Pawson
The human transcription factor CA150 modulates human immunodeficiency virus type 1 gene transcription and contains numerous signaling elements, including six FF domains. Repeated FF domains are...
Donaldson, Ian, Martin, Joel, De Bruijn, Berry, Wolting, Cheryl, Lay, Vicki, Tuekam, Brigitte, ...
Abstract Background The majority of experimentally verified molecular interaction and biological pathway data are present in the unstructured text of biomedical journal articles where they are...
Bidirectional signalling through the EPH-family receptor Nuk and its transmembrane ligands (1996)
Holland, Sacha J., Gale, Nicholas W., Mbamalu, Geraldine, Yancopoulos, George D., Henkemeyer, Mark, Pawson, Tony
Receptor tyrosine kinases of the EPH class have been implicated in the control of axon guidance and fasciculation [1-7], in regulating cell migration [8], and in defining compartments in the...
Bidirectional signalling through the EPH-family receptor Nuk and its transmembrane ligands (1996)
Holland, Sacha J., Gale, Nicholas W., Mbamalu, Geraldine, Yancopoulos, George D., Henkemeyer, Mark, Pawson, Tony
Receptor tyrosine kinases of the EPH class have been implicated in the control of axon guidance and fasciculation [1-7], in regulating cell migration [8], and in defining compartments in the...
Salcini, AE, McGlade, J, Pelicci, G, Nicoletti, I, Pawson, Tony, Pelicci, PG
The mammalian SHC gene encodes three overlapping proteins which all contain a carboxy-terminal SH2 domain. Shc proteins are phosphorylated on tyrosine by a variety of receptor and cytoplasmic...
Salcini, AE, McGlade, J, Pelicci, G, Nicoletti, I, Pawson, Tony, Pelicci, PG
The mammalian SHC gene encodes three overlapping proteins which all contain a carboxy-terminal SH2 domain. Shc proteins are phosphorylated on tyrosine by a variety of receptor and cytoplasmic...
Henkemeyer, M, Marengere, LE, McGlade, J, Olivier, JP, Conlon, RA, Holmyard, DP, ...
Neural kinase (Nuk) encodes a murine receptor-like tyrosine kinase belonging to the Eph/Elk/Eck family. Protein localization studies indicate that during early embryogenesis Nuk is confined to the...
Henkemeyer, M, Marengere, LE, McGlade, J, Olivier, JP, Conlon, RA, Holmyard, DP, ...
Neural kinase (Nuk) encodes a murine receptor-like tyrosine kinase belonging to the Eph/Elk/Eck family. Protein localization studies indicate that during early embryogenesis Nuk is confined to the...
Stephens, RM, Loeb, DM, Copeland, TD, Pawson, Tony, Greene, LA, Kaplan, DR
In response to NGF, the Trk receptor tyrosine kinase forms a complex with SHC, a protein that couples receptor tyrosine kinases to p21ras. Complex formation between Trk and SHC, SHC tyrosine...
Stephens, RM, Loeb, DM, Copeland, TD, Pawson, Tony, Greene, LA, Kaplan, DR
In response to NGF, the Trk receptor tyrosine kinase forms a complex with SHC, a protein that couples receptor tyrosine kinases to p21ras. Complex formation between Trk and SHC, SHC tyrosine...
Crowe, AJ, McGlade, J, Pawson, Tony, Hayman, MJ
The S13 avian erythroblastosis viral genome encodes an oncogenic tyrosine kinase, termed env-sea, that is capable of transforming fibroblasts and erythroblasts. Although the tyrosine kinase activity...
Crowe, AJ, McGlade, J, Pawson, Tony, Hayman, MJ
The S13 avian erythroblastosis viral genome encodes an oncogenic tyrosine kinase, termed env-sea, that is capable of transforming fibroblasts and erythroblasts. Although the tyrosine kinase activity...
SH2 domain specificity and activity modified by a single residue (1994)
Marengere, Luc E. M., Zhou, Songyang, Gerald D., Gish, Schaller, Michael D., Parsons, J. Thomas, Stern, Michael J., ...
Many intracellular targets of protein-tyrosine kinases possess Src homology 2 (SH2) domains that directly recognize phosphotyrosine- containing sites on autophosphorylated growth factor receptors and...
SH2 domain specificity and activity modified by a single residue (1994)
Marengere, Luc E. M., Zhou, Songyang, Gerald D., Gish, Schaller, Michael D., Parsons, J. Thomas, Stern, Michael J., ...
Many intracellular targets of protein-tyrosine kinases possess Src homology 2 (SH2) domains that directly recognize phosphotyrosine- containing sites on autophosphorylated growth factor receptors and...
Regulation of c-Src tyrosine kinase activity by the Src SH2 domainv (1993)
Liu, X, Brodeur, SR, Gish, G, Songyang, Z, Cantley, LC, Laudano, AP, ...
The protein-tyrosine kinase activity of pp60c-src (c-Src) is inhibited by phosphorylation of tyr527, within the c-Src c-terminal tail. Genetic and biochemical data have suggested that this negative...
Regulation of c-Src tyrosine kinase activity by the Src SH2 domainv (1993)
Liu, X, Brodeur, SR, Gish, G, Songyang, Z, Cantley, LC, Laudano, AP, ...
The protein-tyrosine kinase activity of pp60c-src (c-Src) is inhibited by phosphorylation of tyr527, within the c-Src c-terminal tail. Genetic and biochemical data have suggested that this negative...
Olivier, Jean Paul, Raabe, Thomas, Henkerneyer, Mark, Dickson, Barry, Mbamalu, Geraldine, Margolis, Ben, ...
A Drosophila gene (drk) encodes a widely expressed protein with a single SH2 domain and two flanking SH3 domains, which is homologous to the Sem-5 protein of C. elegans and mammalian GRB2. Genetic...
Olivier, Jean Paul, Raabe, Thomas, Henkerneyer, Mark, Dickson, Barry, Mbamalu, Geraldine, Margolis, Ben, ...
A Drosophila gene (drk) encodes a widely expressed protein with a single SH2 domain and two flanking SH3 domains, which is homologous to the Sem-5 protein of C. elegans and mammalian GRB2. Genetic...
Reith, AD, Ellis, C, Maroc, N, Pawson, Tony, Bernstein, A, Dubreuil, P
Point mutations in highly conserved amino acid residues in the catalytic domain of the Kit receptor tyrosine kinase (RTK) are responsible for the coat color, fertility and hematopoietic defects of...
Reith, AD, Ellis, C, Maroc, N, Pawson, Tony, Bernstein, A, Dubreuil, P
Point mutations in highly conserved amino acid residues in the catalytic domain of the Kit receptor tyrosine kinase (RTK) are responsible for the coat color, fertility and hematopoietic defects of...
Veillette, A, Caron, L, Fournel, M, Pawson, Tony
The enzymatic activity of the lymphocyte-specific tyrosine protein kinase p56lck appears to be tightly regulated by phosphorylation of the conserved carboxy-terminal tyrosine residue 505. Indeed,...
Veillette, A, Caron, L, Fournel, M, Pawson, Tony
The enzymatic activity of the lymphocyte-specific tyrosine protein kinase p56lck appears to be tightly regulated by phosphorylation of the conserved carboxy-terminal tyrosine residue 505. Indeed,...
Ellis, C, Liu, XQ, Anderson, D, Abraham, N, Veillette, A, Pawson, Tony
The Ras GTPase activating protein (GAP) is a strong candidate for the protein that links protein-tyrosine kinases to the Ras mitogenic pathway. GAP and two associated proteins, p62 and p190, were...
Ellis, C, Liu, XQ, Anderson, D, Abraham, N, Veillette, A, Pawson, Tony
The Ras GTPase activating protein (GAP) is a strong candidate for the protein that links protein-tyrosine kinases to the Ras mitogenic pathway. GAP and two associated proteins, p62 and p190, were...
Anderson, Deborah, Koch, C. Anne, Grey, Laura, Ellis, Christine, Moran, Michael, Pawson, Tony
Phospholipase Cγ1 (PLCγl) and p21ras guanosine triphosphatase (GTPase) activating protein (GAP) bind to and are phosphorylated by activated growth factor receptors. Both PLCγl and GAP contain two...
Anderson, Deborah, Koch, C. Anne, Grey, Laura, Ellis, Christine, Moran, Michael, Pawson, Tony
Phospholipase Cγ1 (PLCγl) and p21ras guanosine triphosphatase (GTPase) activating protein (GAP) bind to and are phosphorylated by activated growth factor receptors. Both PLCγl and GAP contain two...
Wildenhain, Y, Pawson, Tony, Blackstein, ME, Andrulis, IL
A series of primary human breast tumors was analysed by immunoblotting with anti-neu antibodies. Overproduction of the neu protein-tyrosine kinase, p185neu, was observed in 23 of 56 malignant tumor...
Wildenhain, Y, Pawson, Tony, Blackstein, ME, Andrulis, IL
A series of primary human breast tumors was analysed by immunoblotting with anti-neu antibodies. Overproduction of the neu protein-tyrosine kinase, p185neu, was observed in 23 of 56 malignant tumor...
Ellis, C, Moran, M, McCormick, F, Pawson, Tony
The critical pathways through which protein-tyrosine kinases induce cellular proliferation and malignant transformation are not well defined. As microinjection of antibodies against p21ras can block...
Ellis, C, Moran, M, McCormick, F, Pawson, Tony
The critical pathways through which protein-tyrosine kinases induce cellular proliferation and malignant transformation are not well defined. As microinjection of antibodies against p21ras can block...
Mutational analysis of a phosphotransfer motif essential for v-fps tyrosine kinase activity (1988)
Moran, MF, Koch, CA, Sadowski, I, Pawson, Tony
The catalytic domains of protein-tyrosine kinases such as the P130gag-fps oncoprotein contain the sequence HRDLAARN, followed thirteen residues C-terminal by DFG (P130gag-fps residues 1041-1048 and...
Letwin, K, Yee, SP, Pawson, Tony
A rat brain lambda gt11 cDNA expression library was screened with anti-phosphotyrosine antibody to identify recombinant clones that encode enzymatically active protein-tyrosine kinases. The inserts...
Mutational analysis of a phosphotransfer motif essential for v-fps tyrosine kinase activity (1988)
Moran, MF, Koch, CA, Sadowski, I, Pawson, Tony
The catalytic domains of protein-tyrosine kinases such as the P130gag-fps oncoprotein contain the sequence HRDLAARN, followed thirteen residues C-terminal by DFG (P130gag-fps residues 1041-1048 and...
Letwin, K, Yee, SP, Pawson, Tony
A rat brain lambda gt11 cDNA expression library was screened with anti-phosphotyrosine antibody to identify recombinant clones that encode enzymatically active protein-tyrosine kinases. The inserts...
Sadowski, I, Pawson, Tony, Lagarde, A
The v-fps oncoprotein was expressed in a pre-neoplastic, growth factor-dependent Chinese hamster lung fibroblast line (CCL39) to study its effect on growth controls and on the induction of...
Sadowski, I, Pawson, Tony, Lagarde, A
The v-fps oncoprotein was expressed in a pre-neoplastic, growth factor-dependent Chinese hamster lung fibroblast line (CCL39) to study its effect on growth controls and on the induction of...
Sadowski, Ivan, Stone, James C., Pawson, Tony
Proteins encoded by oncogenes such as v-fpslfes, v-src, v-yes, v-abl, and v-fgr are cytoplasmic protein tyrosine kinases which, unlike transmembrane receptors, are localized to the inside of the...
Sadowski, Ivan, Stone, James C., Pawson, Tony
Proteins encoded by oncogenes such as v-fpslfes, v-src, v-yes, v-abl, and v-fgr are cytoplasmic protein tyrosine kinases which, unlike transmembrane receptors, are localized to the inside of the...
Hock, Björn, Böhme, Beatrix, Karn, Thomas, Yamamoto, Takaharu, Kaibuchi, Kozo, Holtrich, Uwe, ...
Eph-related receptor tyrosine kinases (RTKs) have been implicated in intercellular communication during embryonic development. To elucidate their signal transduction pathways, we applied the yeast...
Morphogenetic movements at gastrulation require the SH2 tyrosine phosphatase Shp2
Saxton, Tracy M., Pawson, Tony
The SH2 domain-containing tyrosine phosphatase Shp2 plays a pivotal role during the gastrulation of vertebrate embryos. However, because of the complex phenotype observed in mouse mutant embryos, the...
The Syk and ZAP-70 SH2-containing tyrosine kinases are implicated in pre-T cell receptor signaling
Cheng, Alec M., Negishi, Izumi, Anderson, Steven J., Chan, Andrew C., Bolen, Joseph, Loh, Dennis Y., ...
An early stage in thymocyte development, after rearrangement of the β chain genes of the T cell receptor (TCR), involves expression of the pre-TCR complex and accompanying differentiation of...
Li, Shun-Cheng, Songyang, Zhou, Vincent, Sébastien J. F., Zwahlen, Catherine, Wiley, Sandra, Cantley, Lewis, ...
The phosphotyrosine-binding (PTB) domain is a recently identified protein module that has been characterized as binding to phosphopeptides containing an NPXpY motif (X = any amino acid). We describe...
Piao, Xianhua, Paulson, Robert, Van der Geer, Peter, Pawson, Tony, Bernstein, Alan
Activating mutations in the Kit receptor tyrosine kinase have been identified in both rodent and human mast cell leukemia. One activating Kit mutation substitutes a valine for aspartic acid at codon...
Role of Syk in B-cell development and antigen-receptor signaling
Cornall, Richard J., Cheng, Alex M., Pawson, Tony, Goodnow, Christopher C.
Antigen receptors (BCRs) on developing B lymphocytes play two opposing roles—promoting survival of cells that may later bind a foreign antigen and inhibiting survival of cells that bind too...
BIND—The Biomolecular Interaction Network Database
Bader, Gary D., Donaldson, Ian, Wolting, Cheryl, Ouellette, B. F. Francis, Pawson, Tony, Hogue, Christopher W. V.
The Biomolecular Interaction Network Database (BIND; http://binddb.org) is a database designed to store full descriptions of interactions, molecular complexes and pathways. Development of the BIND...
Regulation of Early Events in Integrin Signaling by Protein Tyrosine Phosphatase SHP-2
Oh, Eok-Soo, Gu, Haihua, Saxton, Tracy M., Timms, John F., Hausdorff, Sharon, Frevert, Ernst U., ...
The nontransmembrane protein tyrosine phosphatase SHP-2 plays a critical role in growth factor and cytokine signaling pathways. Previous studies revealed that a fraction of SHP-2 moves to focal...
Prasad, Jayendra, Colwill, Karen, Pawson, Tony, Manley, James L.
The splicing of mammalian mRNA precursors requires both protein phosphorylation and dephosphorylation, likely involving modification of members of the SR protein family of splicing factors. Several...
Rauh, Michael J., Blackmore, Valerie, Andrechek, Eran R., Tortorice, Christopher G., Daly, Roger, Lai, Venus Ka-Man, ...
The Grb2 and Shc adapter proteins play critical roles in coupling activated growth factor receptors to several cellular signaling pathways. To assess the role of these molecules in mammary epithelial...
Becker, Elena, Huynh-Do, Uyen, Holland, Sacha, Pawson, Tony, Daniel, Tom O., Skolnik, Edward Y.
The mammalian Ste20 kinase Nck-interacting kinase (NIK) specifically activates the c-Jun amino-terminal kinase (JNK) mitogen-activated protein kinase module. NIK also binds the SH3 domains of the...
Binns, Kathleen L., Taylor, Paul P., Sicheri, Frank, Pawson, Tony, Holland, Sacha J.
Members of the Eph family of receptor tyrosine kinases exhibit a striking degree of amino acid homology, particularly notable in the kinase and membrane-proximal regions. A mutagenesis approach was...
Discoidin Domain Receptor 1 Tyrosine Kinase Has an Essential Role in Mammary Gland Development
Vogel, Wolfgang F., Aszódi, Attila, Alves, Frauke, Pawson, Tony
Various types of collagen have been identified as potential ligands for the two mammalian discoidin domain receptor tyrosine kinases, DDR1 and DDR2. Here, we used a recombinant fusion protein between...
Elowe, Sabine, Holland, Sacha J., Kulkarni, Sarang, Pawson, Tony
Activation of the EphB2 receptor tyrosine kinase by clustered ephrin-B1 induces growth cone collapse and neurite retraction in differentiated NG108 neuronal cells. We have investigated the...
Winberg, Gösta, Matskova, Liudmila, Chen, Fu, Plant, Pamela, Rotin, Daniela, Gish, Gerald, ...
The latent membrane protein (LMP) 2A of Epstein-Barr virus (EBV) is implicated in the maintenance of viral latency and appears to function in part by inhibiting B-cell receptor (BCR) signaling. The...
Kiefer, Friedemann, Brumell, John, Al-Alawi, Nadia, Latour, Sylvain, Cheng, Alec, Veillette, André, ...
The cytoplasmic protein tyrosine kinase Syk has two amino-terminal SH2 domains that engage phosphorylated immunoreceptor tyrosine-based activation motifs in the signaling subunits of immunoreceptors....
C-Terminal Domain of the Epstein-Barr Virus LMP2A Membrane Protein Contains a Clustering Signal
Matskova, Liudmila, Ernberg, Ingemar, Pawson, Tony, Winberg, Gösta
The latency-regulated transmembrane protein LMP2A interferes with signaling from the B-cell antigen receptor by recruiting the tyrosine kinases Lyn and Syk and by targeting them for degradation by...
Epidermolysis bullosa and embryonic lethality in mice lacking the multi-PDZ domain protein GRIP1
Bladt, Friedhelm, Tafuri, Anna, Gelkop, Sigal, Langille, Lowell, Pawson, Tony
Glutamate receptor-interacting protein 1 (GRIP1) is an adaptor protein composed of seven PDZ (postsynaptic density-95/Discs large/zona occludens-1) domains, capable of mediating diverse...
Ong, Siew Hwa, Dilworth, Stephen, Hauck-Schmalenberger, Ingrid, Pawson, Tony, Kiefer, Friedemann
Middle T antigen (PymT) is the principal transforming component of polyomavirus, and rapidly induces hemangiomas in neonatal mice. PymT, a membrane-associated scaffold, recruits and activates Src...
Hwang, Peter M., Li, Chengjun, Morra, Massimo, Lillywhite, Jennifer, Muhandiram, D.Ranjith, Gertler, Frank, ...
The SH2 domain protein SAP/SH2D1A, encoded by the X-linked lymphoproliferative (XLP) syndrome gene, associates with the hematopoietic cell surface receptor SLAM in a phosphorylation-independent...
Park, Eui Kyun, Warner, Neil, Mood, Kathleen, Pawson, Tony, Daar, Ira O.
Low-molecular-weight protein tyrosine phosphatase (LMW-PTP) has been implicated in the regulation of cell growth and actin rearrangement mediated by several receptor tyrosine kinases, including...
Donaldson, Logan W., Gish, Gerald, Pawson, Tony, Kay, Lewis E., Forman-Kay, Julie D.
On phosphorylation of Y221 by Abelson (Abl) kinase, the Crk-II adapter protein undergoes an intramolecular reorganization initiated by the binding of its own Src homology 2 (SH2) domain to the pY221...
Bladt, Friedhelm, Aippersbach, Elke, Gelkop, Sigal, Strasser, Geraldine A., Nash, Piers, Tafuri, Anna, ...
Mammalian Nck1 and Nck2 are closely related adaptor proteins that possess three SH3 domains, followed by an SH2 domain, and are implicated in coupling phosphotyrosine signals to polypeptides that...
Kubiseski, Terrance J., Culotti, Joe, Pawson, Tony
The Caenorhabditis elegans UNC-73B protein regulates axon guidance through its ability to act as a guanine nucleotide exchange factor (GEF) for the CeRAC/MIG-2 GTPases. Like other GEFs for Rho family...
Howard, Perry L., Chia, Marie C., Del Rizzo, Suzanne, Liu, Fei-Fei, Pawson, Tony
Signal transduction pathways are typically controlled by protein–protein interactions, which are mediated by specific modular domains. One hypothetical use of such interaction domains is to...
Multiple modes of peptide recognition by the PTB domain of the cell fate determinant Numb
Zwahlen, Catherine, Li, Shun-Cheng, Kay, Lewis E., Pawson, Tony, Forman-Kay, Julie D.
The phosphotyrosine-binding (PTB) domain of the cell fate determinant Numb is involved in the formation of multiple protein complexes in vivo and can bind a diverse array of peptide sequences in...
The ShcA phosphotyrosine docking protein sensitizes cardiovascular signaling in the mouse embryo
Lai, Ka-Man Venus, Pawson, Tony
The ShcA gene products have served as a model for the analysis of phosphotyrosine-recognition domains, and for the functions of docking proteins during tyrosine kinase signaling. Here we show that...
Saucier, Caroline, Khoury, Hanane, Lai, Ka-Man Venus, Peschard, Pascal, Dankort, David, Naujokas, Monica A., ...
The etiology and progression of a variety of human malignancies are linked to the deregulation of receptor tyrosine kinases (RTKs). To define the role of RTK-dependent signals in various oncogenic...
Dissecting virulence: Systematic and functional analyses of a pathogenicity island
Deng, Wanyin, Puente, José L., Gruenheid, Samantha, Li, Yuling, Vallance, Bruce A., Vázquez, Alejandra, ...
Bacterial pathogenicity islands (PAI) often encode both effector molecules responsible for disease and secretion systems that deliver these effectors to host cells. Human enterohemorrhagic...
Ectopic EphA4 Receptor Induces Posterior Protrusions via FGF Signaling in Xenopus Embryos
Park, Eui Kyun, Warner, Neil, Bong, Yong-Sik, Stapleton, David, Maeda, Ryu, Pawson, Tony, ...
The Eph family of receptor tyrosine kinases regulates numerous biological processes. To examine the biochemical and developmental contributions of specific structural motifs within Eph receptors,...
Kimura, Yuki, Jones, Nina, Klüppel, Michael, Hirashima, Masanori, Tachibana, Kazunobu, Cohn, Jason B., ...
Loss-of-function mutations in the murine dominant white spotting/c-kit locus affect a diverse array of biological processes and cell lineages and cause a range of phenotypes, including severe anemia,...
FF Domains of CA150 Bind Transcription and Splicing Factors through Multiple Weak Interactions
Smith, Matthew J., Kulkarni, Sarang, Pawson, Tony
The human transcription factor CA150 modulates human immunodeficiency virus type 1 gene transcription and contains numerous signaling elements, including six FF domains. Repeated FF domains are...
Troglio, Flavia, Echart, Cinara, Gobbi, Alberto, Pawson, Tony, Pelicci, Pier Giuseppe, De Simoni, Maria Grazia, ...
Rai (Shc C or N-Shc) is a neuron-specific member of the family of Shc-like adaptor proteins. Rai functions in the cytoplasmic propagation of Ret-dependent survival signals and regulates, in vivo, the...
grb2 heterozygosity rescues embryonic lethality but not tumorigenesis in pten+/- mice
Cully, Megan, Elia, Andrew, Ong, Siew-Hwa, Stambolic, Vuk, Pawson, Tony, Tsao, Ming-Sound, ...
PTEN is a tumor suppressor gene implicated in both sporadic cancers and inherited tumor-prone syndromes. Here we show that pten+/- mice display a partially penetrant embryonic lethality. This...
WW Domains Provide a Platform for the Assembly of Multiprotein Networks†
Ingham, Robert J., Colwill, Karen, Howard, Caley, Dettwiler, Sabine, Lim, Caesar S. H., Yu, Joanna, ...
WW domains are protein modules that mediate protein-protein interactions through recognition of proline-rich peptide motifs and phosphorylated serine/threonine-proline sites. To pursue the functional...
Steven, Robert, Zhang, Lijia, Culotti, Joseph, Pawson, Tony
In both Caenorhabditis elegans and Drosophila, UNC-73/Trio functions in axon guidance by signaling through the Rac GTPase to regulate cytoskeletal rearrangements necessary for growth cone migrations....
Colwill, Karen, Wells, Clark D, Elder, Kelly, Goudreault, Marilyn, Hersi, Kadija, Kulkarni, Sarang, ...
Hock, Björn, Böhme, Beatrix, Karn, Thomas, Yamamoto, Takaharu, Kaibuchi, Kozo, Holtrich, Uwe, ...
Eph-related receptor tyrosine kinases (RTKs) have been implicated in intercellular communication during embryonic development. To elucidate their signal transduction pathways, we applied the yeast...
Morphogenetic movements at gastrulation require the SH2 tyrosine phosphatase Shp2
Saxton, Tracy M., Pawson, Tony
The SH2 domain-containing tyrosine phosphatase Shp2 plays a pivotal role during the gastrulation of vertebrate embryos. However, because of the complex phenotype observed in mouse mutant embryos, the...
The Syk and ZAP-70 SH2-containing tyrosine kinases are implicated in pre-T cell receptor signaling
Cheng, Alec M., Negishi, Izumi, Anderson, Steven J., Chan, Andrew C., Bolen, Joseph, Loh, Dennis Y., ...
An early stage in thymocyte development, after rearrangement of the β chain genes of the T cell receptor (TCR), involves expression of the pre-TCR complex and accompanying differentiation of...
Li, Shun-Cheng, Songyang, Zhou, Vincent, Sébastien J. F., Zwahlen, Catherine, Wiley, Sandra, Cantley, Lewis, ...
The phosphotyrosine-binding (PTB) domain is a recently identified protein module that has been characterized as binding to phosphopeptides containing an NPXpY motif (X = any amino acid). We describe...
Piao, Xianhua, Paulson, Robert, Van der Geer, Peter, Pawson, Tony, Bernstein, Alan
Activating mutations in the Kit receptor tyrosine kinase have been identified in both rodent and human mast cell leukemia. One activating Kit mutation substitutes a valine for aspartic acid at codon...
Role of Syk in B-cell development and antigen-receptor signaling
Cornall, Richard J., Cheng, Alex M., Pawson, Tony, Goodnow, Christopher C.
Antigen receptors (BCRs) on developing B lymphocytes play two opposing roles—promoting survival of cells that may later bind a foreign antigen and inhibiting survival of cells that bind too...
BIND—The Biomolecular Interaction Network Database
Bader, Gary D., Donaldson, Ian, Wolting, Cheryl, Ouellette, B. F. Francis, Pawson, Tony, Hogue, Christopher W. V.
The Biomolecular Interaction Network Database (BIND; http://binddb.org) is a database designed to store full descriptions of interactions, molecular complexes and pathways. Development of the BIND...
Regulation of Early Events in Integrin Signaling by Protein Tyrosine Phosphatase SHP-2
Oh, Eok-Soo, Gu, Haihua, Saxton, Tracy M., Timms, John F., Hausdorff, Sharon, Frevert, Ernst U., ...
The nontransmembrane protein tyrosine phosphatase SHP-2 plays a critical role in growth factor and cytokine signaling pathways. Previous studies revealed that a fraction of SHP-2 moves to focal...
Prasad, Jayendra, Colwill, Karen, Pawson, Tony, Manley, James L.
The splicing of mammalian mRNA precursors requires both protein phosphorylation and dephosphorylation, likely involving modification of members of the SR protein family of splicing factors. Several...
Rauh, Michael J., Blackmore, Valerie, Andrechek, Eran R., Tortorice, Christopher G., Daly, Roger, Lai, Venus Ka-Man, ...
The Grb2 and Shc adapter proteins play critical roles in coupling activated growth factor receptors to several cellular signaling pathways. To assess the role of these molecules in mammary epithelial...
Becker, Elena, Huynh-Do, Uyen, Holland, Sacha, Pawson, Tony, Daniel, Tom O., Skolnik, Edward Y.
The mammalian Ste20 kinase Nck-interacting kinase (NIK) specifically activates the c-Jun amino-terminal kinase (JNK) mitogen-activated protein kinase module. NIK also binds the SH3 domains of the...
Binns, Kathleen L., Taylor, Paul P., Sicheri, Frank, Pawson, Tony, Holland, Sacha J.
Members of the Eph family of receptor tyrosine kinases exhibit a striking degree of amino acid homology, particularly notable in the kinase and membrane-proximal regions. A mutagenesis approach was...
Discoidin Domain Receptor 1 Tyrosine Kinase Has an Essential Role in Mammary Gland Development
Vogel, Wolfgang F., Aszódi, Attila, Alves, Frauke, Pawson, Tony
Various types of collagen have been identified as potential ligands for the two mammalian discoidin domain receptor tyrosine kinases, DDR1 and DDR2. Here, we used a recombinant fusion protein between...
Elowe, Sabine, Holland, Sacha J., Kulkarni, Sarang, Pawson, Tony
Activation of the EphB2 receptor tyrosine kinase by clustered ephrin-B1 induces growth cone collapse and neurite retraction in differentiated NG108 neuronal cells. We have investigated the...
Winberg, Gösta, Matskova, Liudmila, Chen, Fu, Plant, Pamela, Rotin, Daniela, Gish, Gerald, ...
The latent membrane protein (LMP) 2A of Epstein-Barr virus (EBV) is implicated in the maintenance of viral latency and appears to function in part by inhibiting B-cell receptor (BCR) signaling. The...
Kiefer, Friedemann, Brumell, John, Al-Alawi, Nadia, Latour, Sylvain, Cheng, Alec, Veillette, André, ...
The cytoplasmic protein tyrosine kinase Syk has two amino-terminal SH2 domains that engage phosphorylated immunoreceptor tyrosine-based activation motifs in the signaling subunits of immunoreceptors....
C-Terminal Domain of the Epstein-Barr Virus LMP2A Membrane Protein Contains a Clustering Signal
Matskova, Liudmila, Ernberg, Ingemar, Pawson, Tony, Winberg, Gösta
The latency-regulated transmembrane protein LMP2A interferes with signaling from the B-cell antigen receptor by recruiting the tyrosine kinases Lyn and Syk and by targeting them for degradation by...
Epidermolysis bullosa and embryonic lethality in mice lacking the multi-PDZ domain protein GRIP1
Bladt, Friedhelm, Tafuri, Anna, Gelkop, Sigal, Langille, Lowell, Pawson, Tony
Glutamate receptor-interacting protein 1 (GRIP1) is an adaptor protein composed of seven PDZ (postsynaptic density-95/Discs large/zona occludens-1) domains, capable of mediating diverse...
Ong, Siew Hwa, Dilworth, Stephen, Hauck-Schmalenberger, Ingrid, Pawson, Tony, Kiefer, Friedemann
Middle T antigen (PymT) is the principal transforming component of polyomavirus, and rapidly induces hemangiomas in neonatal mice. PymT, a membrane-associated scaffold, recruits and activates Src...
Hwang, Peter M., Li, Chengjun, Morra, Massimo, Lillywhite, Jennifer, Muhandiram, D.Ranjith, Gertler, Frank, ...
The SH2 domain protein SAP/SH2D1A, encoded by the X-linked lymphoproliferative (XLP) syndrome gene, associates with the hematopoietic cell surface receptor SLAM in a phosphorylation-independent...
Park, Eui Kyun, Warner, Neil, Mood, Kathleen, Pawson, Tony, Daar, Ira O.
Low-molecular-weight protein tyrosine phosphatase (LMW-PTP) has been implicated in the regulation of cell growth and actin rearrangement mediated by several receptor tyrosine kinases, including...
Donaldson, Logan W., Gish, Gerald, Pawson, Tony, Kay, Lewis E., Forman-Kay, Julie D.
On phosphorylation of Y221 by Abelson (Abl) kinase, the Crk-II adapter protein undergoes an intramolecular reorganization initiated by the binding of its own Src homology 2 (SH2) domain to the pY221...
Bladt, Friedhelm, Aippersbach, Elke, Gelkop, Sigal, Strasser, Geraldine A., Nash, Piers, Tafuri, Anna, ...
Mammalian Nck1 and Nck2 are closely related adaptor proteins that possess three SH3 domains, followed by an SH2 domain, and are implicated in coupling phosphotyrosine signals to polypeptides that...
Kubiseski, Terrance J., Culotti, Joe, Pawson, Tony
The Caenorhabditis elegans UNC-73B protein regulates axon guidance through its ability to act as a guanine nucleotide exchange factor (GEF) for the CeRAC/MIG-2 GTPases. Like other GEFs for Rho family...
Howard, Perry L., Chia, Marie C., Del Rizzo, Suzanne, Liu, Fei-Fei, Pawson, Tony
Signal transduction pathways are typically controlled by protein–protein interactions, which are mediated by specific modular domains. One hypothetical use of such interaction domains is to...
Multiple modes of peptide recognition by the PTB domain of the cell fate determinant Numb
Zwahlen, Catherine, Li, Shun-Cheng, Kay, Lewis E., Pawson, Tony, Forman-Kay, Julie D.
The phosphotyrosine-binding (PTB) domain of the cell fate determinant Numb is involved in the formation of multiple protein complexes in vivo and can bind a diverse array of peptide sequences in...
The ShcA phosphotyrosine docking protein sensitizes cardiovascular signaling in the mouse embryo
Lai, Ka-Man Venus, Pawson, Tony
The ShcA gene products have served as a model for the analysis of phosphotyrosine-recognition domains, and for the functions of docking proteins during tyrosine kinase signaling. Here we show that...
Saucier, Caroline, Khoury, Hanane, Lai, Ka-Man Venus, Peschard, Pascal, Dankort, David, Naujokas, Monica A., ...
The etiology and progression of a variety of human malignancies are linked to the deregulation of receptor tyrosine kinases (RTKs). To define the role of RTK-dependent signals in various oncogenic...
Dissecting virulence: Systematic and functional analyses of a pathogenicity island
Deng, Wanyin, Puente, José L., Gruenheid, Samantha, Li, Yuling, Vallance, Bruce A., Vázquez, Alejandra, ...
Bacterial pathogenicity islands (PAI) often encode both effector molecules responsible for disease and secretion systems that deliver these effectors to host cells. Human enterohemorrhagic...
Ectopic EphA4 Receptor Induces Posterior Protrusions via FGF Signaling in Xenopus Embryos
Park, Eui Kyun, Warner, Neil, Bong, Yong-Sik, Stapleton, David, Maeda, Ryu, Pawson, Tony, ...
The Eph family of receptor tyrosine kinases regulates numerous biological processes. To examine the biochemical and developmental contributions of specific structural motifs within Eph receptors,...
Kimura, Yuki, Jones, Nina, Klüppel, Michael, Hirashima, Masanori, Tachibana, Kazunobu, Cohn, Jason B., ...
Loss-of-function mutations in the murine dominant white spotting/c-kit locus affect a diverse array of biological processes and cell lineages and cause a range of phenotypes, including severe anemia,...
FF Domains of CA150 Bind Transcription and Splicing Factors through Multiple Weak Interactions
Smith, Matthew J., Kulkarni, Sarang, Pawson, Tony
The human transcription factor CA150 modulates human immunodeficiency virus type 1 gene transcription and contains numerous signaling elements, including six FF domains. Repeated FF domains are...
Troglio, Flavia, Echart, Cinara, Gobbi, Alberto, Pawson, Tony, Pelicci, Pier Giuseppe, De Simoni, Maria Grazia, ...
Rai (Shc C or N-Shc) is a neuron-specific member of the family of Shc-like adaptor proteins. Rai functions in the cytoplasmic propagation of Ret-dependent survival signals and regulates, in vivo, the...
grb2 heterozygosity rescues embryonic lethality but not tumorigenesis in pten+/- mice
Cully, Megan, Elia, Andrew, Ong, Siew-Hwa, Stambolic, Vuk, Pawson, Tony, Tsao, Ming-Sound, ...
PTEN is a tumor suppressor gene implicated in both sporadic cancers and inherited tumor-prone syndromes. Here we show that pten+/- mice display a partially penetrant embryonic lethality. This...
WW Domains Provide a Platform for the Assembly of Multiprotein Networks†
Ingham, Robert J., Colwill, Karen, Howard, Caley, Dettwiler, Sabine, Lim, Caesar S. H., Yu, Joanna, ...
WW domains are protein modules that mediate protein-protein interactions through recognition of proline-rich peptide motifs and phosphorylated serine/threonine-proline sites. To pursue the functional...
Steven, Robert, Zhang, Lijia, Culotti, Joseph, Pawson, Tony
In both Caenorhabditis elegans and Drosophila, UNC-73/Trio functions in axon guidance by signaling through the Rac GTPase to regulate cytoskeletal rearrangements necessary for growth cone migrations....
Colwill, Karen, Wells, Clark D, Elder, Kelly, Goudreault, Marilyn, Hersi, Kadija, Kulkarni, Sarang, ...
Smith, Matthew J., Hardy, W. Rod, Murphy, James M., Jones, Nina, Pawson, Tony
Modular interaction domains that recognize peptide motifs in target proteins can impart selectivity in signaling pathways. Phosphotyrosine binding (PTB) domains are components of cytoplasmic docking...
A change in conformational dynamics underlies the activation of Eph receptor tyrosine kinases
Wiesner, Silke, Wybenga-Groot, Leanne E, Warner, Neil, Lin, Hong, Pawson, Tony, Forman-Kay, Julie D, ...
Eph receptor tyrosine kinases (RTKs) mediate numerous developmental processes. Their activity is regulated by auto-phosphorylation on two tyrosines within the juxtamembrane segment (JMS) immediately...
Analysis of a Shc Family Adaptor Protein, ShcD/Shc4, That Associates with Muscle-Specific Kinase▿
Jones, Nina, Hardy, W. Rod, Friese, Matthew B., Jorgensen, Claus, Smith, Matthew J., Woody, Neil M., ...
Shc family proteins serve as phosphotyrosine adaptor molecules in various receptor-mediated signaling pathways. In mammals, three distinct Shc genes have been described that encode proteins...
Polyelectrostatic interactions of disordered ligands suggest a physical basis for ultrasensitivity
Borg, Mikael, Mittag, Tanja, Pawson, Tony, Tyers, Mike, Forman-Kay, Julie D., Chan, Hue Sun
Regulation of biological processes often involves phosphorylation of intrinsically disordered protein regions, thereby modulating protein interactions. Initiation of DNA replication in yeast requires...
Seet, Bruce T, Berry, Donna M, Maltzman, Jonathan S, Shabason, Jacob, Raina, Monica, Koretzky, Gary A, ...
The relationship between the binding affinity and specificity of modular interaction domains is potentially important in determining biological signaling responses. In signaling from the T-cell...
NetworKIN: a resource for exploring cellular phosphorylation networks
Linding, Rune, Jensen, Lars Juhl, Pasculescu, Adrian, Olhovsky, Marina, Colwill, Karen, Bork, Peer, ...
Protein kinases control cellular responses by phosphorylating specific substrates. Recent proteome-wide mapping of protein phosphorylation sites by mass spectrometry has discovered thousands of in...
Murphy, James M., Korzhnev, Dmitry M., Ceccarelli, Derek F., Briant, Douglas J., Zarrine-Afsar, Arash, Sicheri, Frank, ...
The Par-1/MARK protein kinases play a pivotal role in establishing cellular polarity. This family of kinases contains a unique domain architecture, in which a ubiquitin-associated (UBA) domain is...
Campellone, Kenneth G., Rankin, Susannah, Pawson, Tony, Kirschner, Marc W., Tipper, Donald J., Leong, John M.
Enteropathogenic Escherichia coli (EPEC) translocates effector proteins into mammalian cells to promote reorganization of the cytoskeleton into filamentous actin pedestals. One effector, Tir, is a...
c-Abl phosphorylates Dok1 to promote filopodia during cell spreading
Woodring, Pamela J., Meisenhelder, Jill, Johnson, Sam A., Zhou, Guo-Lei, Field, Jeffrey, Shah, Kavita, ...
Filopodia are dynamic F-actin structures that cells use to explore their environment. c-Abl tyrosine kinase promotes filopodia during cell spreading through an unknown mechanism that does not require...
Cytokine Signaling and Hematopoietic Homeostasis Are Disrupted in Lnk-deficient Mice
Velazquez, Laura, Cheng, Alec M., Fleming, Heather E., Furlonger, Caren, Vesely, Shirly, Bernstein, Alan, ...
The adaptor protein Lnk, and the closely related proteins APS and SH2B, form a subfamily of SH2 domain-containing proteins implicated in growth factor, cytokine, and immunoreceptor signaling. To...
Role of P120 Ras-Gap in Directed Cell Movement
Kulkarni, Sarang V., Gish, Gerald, Van Der Geer, Peter, Henkemeyer, Mark, Pawson, Tony
We have used cell lines deficient in p120 Ras GTPase activating protein (Ras-GAP) to investigate the roles of Ras-GAP and the associated p190 Rho-GAP (p190) in cell polarity and cell migration. Cell...
Blasutig, Ivan M., New, Laura A., Thanabalasuriar, Ajitha, Dayarathna, Thamara K., Goudreault, Marilyn, Quaggin, Susan E., ...
We have analyzed the means by which the Nck family of adaptor proteins couples adhesion proteins to actin reorganization. The nephrin adhesion protein is essential for the formation of actin-based...
Nck adaptor proteins control the organization of neuronal circuits important for walking
Fawcett, James P., Georgiou, John, Ruston, Julie, Bladt, Friedhelm, Sherman, Andrew, Warner, Neil, ...
The intracellular signaling targets used by mammalian axon guidance receptors to organize the nervous system in vivo are unclear. The Nck1 and Nck2 SH2/SH3 adaptors (collectively Nck) can couple...
Germline EPHB2 Receptor Variants in Familial Colorectal Cancer
Zogopoulos, George, Jorgensen, Claus, Bacani, Julinor, Montpetit, Alexandre, Lepage, Pierre, Ferretti, Vincent, ...
Familial clustering of colorectal cancer occurs in 15–20% of cases, however recognized cancer syndromes explain only a small fraction of this disease. Thus, the genetic basis for the majority of...
Filippakopoulos, Panagis, Kofler, Michael, Hantschel, Oliver, Gish, Gerald D., Grebien, Florian, Salah, Eidarus, ...
The SH2 domain of cytoplasmic tyrosine kinases can enhance catalytic activity and substrate recognition, but the molecular mechanisms by which this is achieved are poorly understood. We have solved...
Protein phosphatase 1 regulates the phosphorylation state of the polarity scaffold Par-3
Traweger, Andreas, Wiggin, Giselle, Taylor, Lorne, Tate, Stephen A., Metalnikov, Pavel, Pawson, Tony
Phosphorylation of the polarity protein Par-3 by the serine/threonine kinases aPKCζ/ι and Par-1 (EMK1/MARK2) regulates various aspects of epithelial cell polarity, but little is known about the...
Sonnberg, Stephanie, Seet, Bruce T., Pawson, Tony, Fleming, Stephen B., Mercer, Andrew A.
F-box proteins direct the degradation of an extensive range of proteins via the ubiquitin-proteasome system. Members of this large family of proteins are typically bipartite. They recruit specific...
ShcA signalling is essential for tumour progression in mouse models of human breast cancer
Ursini-Siegel, Josie, Hardy, W Rod, Zuo, Dongmei, Lam, Sonya H L, Sanguin-Gendreau, Virginie, Cardiff, Robert D, ...
To explore the in vivo significance of ShcA during mammary tumorigenesis, we used mice expressing several phosphotyrosine-deficient ShcA alleles under the control of their endogenous promoter. We...
To, Ciric, Kulkarni, Sarang, Pawson, Tony, Honda, Tadashi, Gribble, Gordon W., Sporn, Michael B., ...
The anti-tumor synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO)-imidazolide (CDDO-Im) ectopically activates the transforming growth factor β (TGFβ)-Smad pathway and...