EphB receptor activity suppresses colorectal cancer progression (2005)
Batlle, E., Bacani, J., Begthel, H., Jonkeer, S., Gregorieff, A., Born, M. Van De, ...
The Biomolecular Interaction Network Database and related tools 2005 update (2005)
Alfarano, C., Andrade, C. E., Anthony, K., Bahroos, N., Bajec, M., Bantoft, K., ...
The Biomolecular Interaction Network Database (BIND) (http://bind.ca) archives biomolecular interaction, reaction, complex and pathway information. Our aim is to curate the details about molecular...
C. Alfarano, C. E. Andrade, K. Anthony, N. Bahroos, M. Bajec, K. Bantoft, ...
The Biomolecular Interaction Network Database (BIND)
Biochemical and genetic analysis of the Drk SH2/SH3 adaptor protein of Drosophila. (1995)
Raabe, T, Olivier, J P, Dickson, B J, Liu, X, Gish, G D, Pawson, T, ...
The Drk SH3-SH2-SH3 adaptor protein has been genetically identified in a screen for rate-limiting components acting downstream of the Sevenless (Sev) receptor tyrosine kinase in the developing eye of...
Feng, G-S, Shen, R, Heng, HHQ, Tsui, L-C, Kazlauskas, A, Pawson, T
The murine phosphotyrosine phosphatase, Syp, is a widely-expressed cytoplasmic enzyme that contains two SH2 domains. Syp is physically associated with activated receptors for epidermal growth factor...
Disruption of epithelial gamma delta T cell repertoires by mutation of the Syk tyrosine kinase.
Mallick-Wood, C A, Pao, W, Cheng, A M, Lewis, J M, Kulkarni, S, Bolen, J B, ...
Chimeric mice in which lymphocytes are deficient in the Syk tyrosine kinase have been created. Compared with Syk-positive controls, mice with Syk -/- lymphocytes display substantial depletion of...
O'Bryan, J P, Songyang, Z, Cantley, L, Der, C J, Pawson, T
The Shc adaptor protein, hereafter referred to as ShcA, possesses two distinct phosphotyrosine-recognition modules, a C-terminal Src homology 2 (SH2) domain and an N-terminal phosphotyrosine-binding...
Wiley, S, Gish, G D, Lai, V K, Stephens, R, White, M F, ...
The Shc adaptor protein contains two phosphotyrosine [Tyr(P)]binding modules--an N-terminal Tyr(P) binding (PTB) domain and a C-terminal Src homology 2 (SH2) domain. We have compared the ability of...
Payne, G, Shoelson, S E, Gish, G D, Pawson, T, Walsh, C T
Src homology 2 (SH2) domains are phosphotyrosine-binding modules found within various signal-transducing proteins. We have determined by 125I competition assay and surface plasmon resonance that the...
Kazlauskas, A, Feng, G S, Pawson, T, Valius, M
Ligand-stimulated autophosphorylation of the platelet-derived growth factor receptor (PDGFR) beta subunit creates a number of binding sites for SH2-containing proteins. One of the PDGFR-associated...
Shc proteins are phosphorylated and regulated by the v-Src and v-Fps protein-tyrosine kinases.
McGlade, J, Cheng, A, Pelicci, G, Pelicci, P G, Pawson, T
The mammalian shc gene encodes two overlapping proteins of 46 and 52 kDa, each with a C-terminal Src homology 2 (SH2) domain and an N-terminal glycine/proline-rich sequence, that induce malignant...
Src homology region 2 domains direct protein-protein interactions in signal transduction.
Moran, M F, Koch, C A, Anderson, D, Ellis, C, England, L, Martin, G S, ...
Cytoplasmic proteins that regulate signal transduction or induce cellular transformation, including cytoplasmic protein-tyrosine kinases, p21ras GTPase-activating protein (GAP), phospholipase C...
Liu, X J, Sorisky, A, Zhu, L, Pawson, T
An insulin receptor substrate 1 (IRS-1)-like cDNA was isolated from a Xenopus ovary cDNA library by low-stringency hybridization using rat IRS-1 cDNA as a probe. The deduced amino acid sequence...
A Drosophila shc gene product is implicated in signaling by the DER receptor tyrosine kinase.
Lai, K M, Olivier, J P, Gish, G D, Henkemeyer, M, McGlade, J, Pawson, T
Antibodies to the human Shc adaptor protein were used to isolate a cDNA encoding a Drosophila Shc protein (dShc) by screening an expression library. The dshc gene, which maps to position 67B-C on the...
Aberrant Ras regulation and reduced p190 tyrosine phosphorylation in cells lacking p120-Gap.
Henkemeyer, M, Jacks, T, Pawson, T
The Ras guanine nucleotide-binding protein functions as a molecular switch in signalling downstream of protein-tyrosine kinases. Ras is activated by exchange of GDP for GTP and is turned off by...
Early-passage rat adrenocortical cells were infected with Kirsten murine sarcoma virus and MMCV mouse myc virus, two retroviruses carrying the v-Ki-ras and v-myc oncogenes, respectively. Efficient...
Monoclonal antibodies reactive with either gag or fps portions of the wild-type Fujinami sarcoma virus transforming protein have been used to probe the structure of proteins encoded by mutant genomes...
Weinmaster, G, Hinze, E, Pawson, T
The phosphorylation sites of the P140gag-fps gene product of Fujinami avian sarcoma virus have been identified and localized to different regions of this transforming protein. FSV P140gag-fps...
Ingman-Baker, J, Hinze, E, Levy, J G, Pawson, T
Two monoclonal antibodies have been obtained that recognize antigenic determinants within the C-terminal fps-encoded region of P140gag-fps, the transforming protein of Fujinami avian sarcoma virus...
Structure and phosphorylation of the Fujinami sarcoma virus gene product.
Pawson, T, Kung, T H, Martin, G S
The Fujinami avian sarcoma virus (FSV) transforming gene product, P140, is a fusion protein which contains both gag-related and FSV-specific methionine-containing tryptic peptides. The virion...
Stern, M J, Marengere, L E, Daly, R J, Lowenstein, E J, Kokel, M, Batzer, A, ...
Mutations in the Caenorhabditis elegans gene sem-5 affect cell signaling processes involved in guiding a class of cell migrations and inducing vulval cell fates. The sem-5 sequence encodes a protein...
env Gene of Rous sarcoma virus: identification of the gene product by cell-free translation.
Pawson, T, Mellon, P, Duesberg, P H, Martin, G S
Cell-free translation of polyadenylic acid-selected, denatured virion 70S RNA of the Schmidt-Ruppin strain of Rous sarcoma virus (subgroup A) yields a 64,000-Mr polypeptide which is specifically...
Cell-free translation of avian erythroblastosis virus RNA.
Avian erythroblastosis virus (AEV) RNA rescued from nonproducer cells by superinfection with a helper virus is translated into three polypeptides in the messenger-dependent rabbit reticulocyte...
Cardiac and neurological abnormalities in v-fps transgenic mice.
Yee, S P, Mock, D, Maltby, V, Silver, M, Rossant, J, Bernstein, A, ...
Transgenic mice that widely express the v-fps protein-tyrosine kinase develop several independent pathological conditions, in addition to a high tumor incidence. v-fps expression and protein-tyrosine...
A conserved domain regulates interactions of the v-fps protein-tyrosine kinase with the host cell.
DeClue, J E, Sadowski, I, Martin, G S, Pawson, T
All cytoplasmic protein-tyrosine kinases (PTKs) share a noncatalytic domain, termed SH2, which comprises approximately 100 residues located immediately N-terminal to the kinase domain. A linker in...
Pawson, T, Martin, G S, Smith, A E
Nondefective and transformation-defective virion subunit RNAs from two strains of Rous sarcoma virus (RSV) were translated in cell-free systems derived from Krebs IIA ascites cells, wheat germ, and...
Specific motifs recognized by the SH2 domains of Csk, 3BP2, fps/fes, GRB-2, HCP, SHC, Syk, and Vav.
Songyang, Z, Shoelson, S E, McGlade, J, Olivier, P, Pawson, T, Bustelo, X R, ...
Src homology 2 (SH2) domains provide specificity to intracellular signaling by binding to specific phosphotyrosine (phospho-Tyr)-containing sequences. We recently developed a technique using a...
Panayotou, G, Gish, G, End, P, Truong, O, Gout, I, Dhand, R, ...
The interaction between SH2 domains and phosphotyrosine-containing sequences was examined by real-time measurements of kinetic parameters. The SH2 domains of the p85 subunit of the...
Moran, M F, Polakis, P, McCormick, F, Pawson, T, Ellis, C
The p21ras GTPase-activating protein (GAP) down-regulates p21ras by stimulating its intrinsic GTPase activity. GAP is found predominantly as a monomer in the cytosol of normal cells. However, in...
Sultzman, L, Ellis, C, Lin, L L, Pawson, T, Knopf, J
Upon binding to its cell surface receptor, platelet-derived growth factor (PDGF) causes the tyrosine phosphorylation of phospholipase C-gamma 1 (PLC-gamma 1) and stimulates the production of...
Characterization of elk, a brain-specific receptor tyrosine kinase.
Lhoták, V, Greer, P, Letwin, K, Pawson, T
The elk gene encodes a novel receptorlike protein-tyrosine kinase, which belongs to the eph subfamily. We have previously identified a partial cDNA encompassing the elk catalytic domain (K. Letwin,...
GTPase-activating protein (GAP) stimulates the ability of p21ras to hydrolyze GTP to GDP. Since GAP is phosphorylated by a variety of activated or oncogenic protein-tyrosine kinases, it may couple...
Rottapel, R, Reedijk, M, Williams, D E, Lyman, S D, Anderson, D M, Pawson, T, ...
The W/c-kit and Steel loci respectively encode a receptor tyrosine kinase (Kit) and its extracellular ligand, Steel factor, which are essential for the development of hematopoietic, melanocyte, and...
The v-Src SH3 domain binds phosphatidylinositol 3'-kinase.
Liu, X, Marengere, L E, Koch, C A, Pawson, T
Fibroblasts transformed by v-src or by related oncogenes encoding activated tyrosine kinases contain elevated levels of polyphosphoinositides with phosphate at the D-3 position of the inositol ring,...
Suen, K L, Bustelo, X R, Pawson, T, Barbacid, M
We report the isolation and molecular characterization of the mouse grb2 gene. The product of this gene, the Grb2 protein, is highly related to the Caenorhabditis elegans sem-5 gene product and the...
Muller, A J, Pendergast, A M, Havlik, M H, Puil, L, Pawson, T, Witte, O N
SH2 (src homology region 2) domains are implicated in protein-protein interactions involved in signal transduction pathways. Isolated SH2 domains bind proteins that are tyrosine phosphorylated. A...
Mutational activation of c-raf-1 and definition of the minimal transforming sequence.
Heidecker, G, Huleihel, M, Cleveland, J L, Kolch, W, Beck, T W, Lloyd, P, ...
A series of wild-type and mutant raf genes was transfected into NIH 3T3 cells and analyzed for transforming activity. Full-length wild-type c-raf did not show transforming activity. Two types of...
Myeloid expression of the human c-fps/fes proto-oncogene in transgenic mice.
Greer, P, Maltby, V, Rossant, J, Bernstein, A, Pawson, T
The mammalian c-fps/fes proto-oncogene encodes a 92-kilodalton cytoplasmic protein-tyrosine kinase (p92c-fes), which is expressed in immature and differentiated hematopoietic cells of the myeloid...
Reedijk, M, Liu, X Q, Pawson, T
The interactions of the macrophage colony-stimulating factor 1 (CSF-1) receptor with potential targets were investigated after ligand stimulation either of mouse macrophages or of fibroblasts that...
Lavigueur, A, Maltby, V, Mock, D, Rossant, J, Pawson, T, Bernstein, A
We have investigated the role of the p53 gene in oncogenesis in vivo by generating transgenic mice carrying murine p53 genomic fragments isolated from a mouse Friend erythroleukemia cell line or...
Koch, C A, Moran, M, Sadowski, I, Pawson, T
A conserved noncatalytic domain SH2 (for src homology region 2) is located immediately N terminal to the kinase domains of all cytoplasmic protein-tyrosine kinases. We found that the wild-type v-fps...
Brooks-Wilson, A R, Ball, E, Pawson, T
The P130gag-fps protein-tyrosine kinase of Fujinami sarcoma virus contains an N-terminal fps-specific domain (Nfps) that is important for oncogenicity. The N-terminal 14 amino acids of p60v-src,...
Greer, P A, Meckling-Hansen, K, Pawson, T
A 13-kilobase EcoRI genomic restriction fragment containing the human c-fps/fes proto-oncogene locus was expressed transiently in Cos-1 monkey cells and stably in Rat-2 fibroblasts. In both cases,...
Edwards, A M, Arquint, M, Braun, P E, Roder, J C, Dunn, R J, Pawson, T, ...
Myelin-associated glycoprotein (MAG) has been implicated in the mediation of interactions between oligodendrocytes and neurons during the development of the myelin sheath. Here we show that MAG is...
Lymphoid and mesenchymal tumors in transgenic mice expressing the v-fps protein-tyrosine kinase.
Yee, S P, Mock, D, Greer, P, Maltby, V, Rossant, J, Bernstein, A, ...
src, abl, and fps/fes are prototypes for a family of genes encoding nonreceptor protein-tyrosine kinases. The oncogenic potential of the v-fps protein-tyrosine kinase was investigated by introduction...
Pawson, T, Letwin, K, Lee, T, Hao, Q L, Heisterkamp, N, Groffen, J
We have recently isolated human and rat cDNAs (designated FER and flk, respectively) which encode nonreceptor protein-tyrosine kinases which are very similar to one another and related in sequence...
Multiple cDNAs encoding the esk kinase predict transmembrane and intracellular enzyme isoforms.
Douville, E M, Afar, D E, Howell, B W, Letwin, K, Tannock, L, Ben-David, Y, ...
A novel protein kinase, the Esk kinase, has been isolated from an embryonal carcinoma (EC) cell line by using an expression cloning strategy. Sequence analysis of two independent cDNA clones (2.97...
Caron, L, Abraham, N, Pawson, T, Veillette, A
To understand the mechanism(s) by which p56lck participates in T-cell receptor (TCR) signalling, we have examined the effects of mutations in known regulatory domains of p56lck on the ability of F505...
Eph, Elk, and Eck are prototypes of a large family of transmembrane protein-tyrosine kinases, which are characterized by a highly conserved cysteine-rich domain and two fibronectin type III repeats...
Regulation of a ras-related protein during development of Dictyostelium discoideum.
Pawson, T, Amiel, T, Hinze, E, Auersperg, N, Neave, N, Sobolewski, A, ...
Recent work has shown that DNA sequences related to the mammalian ras proto-oncogenes are highly conserved in eucaryotic evolution. A monoclonal antibody (Y13-259) to mammalian p21ras specifically...
MacDonald, I, Levy, J, Pawson, T
The avian c-fps and mammalian c-fes proto-oncogenes are cognate cellular sequences. Antiserum raised against the P140gag-fps transforming protein of Fujinami avian sarcoma virus specifically...
Sadowski, I, Stone, J C, Pawson, T
Proteins encoded by oncogenes such as v-fps/fes, 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...
MacAuley, A, Auersperg, N, Pawson, T
Rat adrenal cortex cells infected with Kirsten murine sarcoma virus acquire a transformed phenotype in a progressive fashion. The expression of the viral p21ras does not appear to correlate with the...
Multiple SH2-mediated interactions in v-src-transformed cells.
Koch, C A, Moran, M F, Anderson, D, Liu, X Q, Mbamalu, G, Pawson, T
The Src homology 2 (SH2) domain is a noncatalytic region which is conserved among a number of signaling and transforming proteins, including cytoplasmic protein-tyrosine kinases and Ras...
Bcr-Abl oncoproteins bind directly to activators of the Ras signalling pathway.
Puil, L, Liu, J, Gish, G, Mbamalu, G, Bowtell, D, Pelicci, P G, ...
The cytosolic 185 and 210 kDa Bcr-Abl protein tyrosine kinases play important roles in the development of Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia (CML) and acute...
Biochemical and genetic analysis of the Drk SH2/SH3 adaptor protein of Drosophila.
Raabe, T, Olivier, J P, Dickson, B, Liu, X, Gish, G D, Pawson, T, ...
The Drk SH3-SH2-SH3 adaptor protein has been genetically identified in a screen for rate-limiting components acting downstream of the Sevenless (Sev) receptor tyrosine kinase in the developing eye of...
Taylor, G R, Reedijk, M, Rothwell, V, Rohrschneider, L, Pawson, T
The receptors for colony stimulating factor-1 (CSF-1), platelet derived growth factor and the c-kit protein tyrosine kinase (PTK) contain within their catalytic domains a stretch of 60-100 residues,...
The N-terminal region of GAP regulates cytoskeletal structure and cell adhesion.
McGlade, J, Brunkhorst, B, Anderson, D, Mbamalu, G, Settleman, J, Dedhar, S, ...
Ras GTPase activating protein (GAP) possesses a C-terminal domain that interacts with GTP-bound Ras, and an N-terminal region containing two SH2 domains and an SH3 domain. In addition to its...
Colwill, K, Pawson, T, Andrews, B, Prasad, J, Manley, J L, Bell, J C, ...
Mammalian Clk/Sty is the prototype for a family of dual specificity kinases (termed LAMMER kinases) that have been conserved in evolution, but whose physiological substrates are unknown. In a yeast...
Roche, S, McGlade, J, Jones, M, Gish, G D, Pawson, T, Courtneidge, S A
We have investigated the roles of the phosphotyrosine phosphatase Syp (also called SH-PTP2), phospholipase C (PLC) gamma1, rasGTPase Activating Protein (rasGAP) and the adapter molecules Nck and Shc...
Sek4 and Nuk receptors cooperate in guidance of commissural axons and in palate formation.
Orioli, D, Henkemeyer, M, Lemke, G, Klein, R, Pawson, T
Sek4 and Nuk are members of the Eph-related family of receptor protein-tyrosine kinases. These receptors interact with a set of cell surface ligands that have recently been implicated in axon...
HPK1, a hematopoietic protein kinase activating the SAPK/JNK pathway.
Kiefer, F, Tibbles, L A, Anafi, M, Janssen, A, Zanke, B W, Lassam, N, ...
In mammalian cells, a specific stress-activated protein kinase (SAPK/JNK) pathway is activated in response to inflammatory cytokines, injury from heat, chemotherapeutic drugs and UV or ionizing...
Ben-David, Y, Letwin, K, Tannock, L, Bernstein, A, Pawson, T
In a screen of mouse erythroleukemia cDNA expression libraries with anti-phosphotyrosine antibodies, designed to isolate tyrosine kinase coding sequences, we identified several cDNAs encoding...
Signal transduction by normal isoforms and W mutant variants of the Kit receptor tyrosine kinase.
Reith, A D, Ellis, C, Lyman, S D, Anderson, D M, Williams, D E, Bernstein, A, ...
Germline mutations at the Dominant White Spotting (W) and Steel (Sl) loci have provided conclusive genetic evidence that c-kit mediated signal transduction pathways are essential for normal mouse...
The Biomolecular Interaction Network Database and related tools 2005 update
Alfarano, C., Andrade, C. E., Anthony, K., Bahroos, N., Bajec, M., Bantoft, K., ...
The Biomolecular Interaction Network Database (BIND) (http://bind.ca) archives biomolecular interaction, reaction, complex and pathway information. Our aim is to curate the details about molecular...
Margolis, B, Li, N, Koch, A, Mohammadi, M, Hurwitz, D R, Zilberstein, A, ...
Phospholipase C-gamma (PLC-gamma) and GTPase activating protein (GAP) are substrates of EGF, PDGF and other growth factor receptors. Since either PLC-gamma or GAP also bind to the activated receptors...
Meckling-Hansen, K, Nelson, R, Branton, P, Pawson, T
Site-directed mutagenesis of the Fujinami sarcoma virus (FSV) genome has suggested that Tyr 1073 of the P130gag--fps protein-tyrosine kinase is a regulatory site. To investigate directly the ability...
Reedijk, M, Liu, X, Letwin, K, Waterfield, M D, Hunter, T, ...
Efficient binding of active phosphatidylinositol (PI) 3'-kinase to the autophosphorylated macrophage colony stimulating factor receptor (CSF-1R) requires the noncatalytic kinase insert (KI) region of...
Letwin, K, Mizzen, L, Motro, B, Ben-David, Y, Bernstein, A, Pawson, T
Screening of mouse cDNA expression libraries with antibodies to phosphotyrosine resulted in repeated isolation of cDNAs that encode a novel mammalian protein kinase of 774 amino acids, termed Nek1....
A lysine in the ATP-binding site of P130gag-fps is essential for protein-tyrosine kinase activity.
Weinmaster, G, Zoller, M J, Pawson, T
The P130gag-fps transforming protein of Fujinami sarcoma virus (FSV) possesses tyrosine-specific protein kinase activity and autophosphorylates at Tyr-1073. Within the kinase domain of P130gag-fps is...
Migliaccio, E, Mele, S, Salcini, A E, Pelicci, G, Lai, K M, Superti-Furga, G, ...
Shc proteins are targets of activated tyrosine kinases and are implicated in the transmission of activation signals to Ras. The p46shc and p52shc isoforms share a C-terminal SH2 domain, a proline-...
Abnormal mesoderm patterning in mouse embryos mutant for the SH2 tyrosine phosphatase Shp-2.
Saxton, T M, Henkemeyer, M, Gasca, S, Shen, R, Rossi, D J, Shalaby, F, ...
Shp-1, Shp-2 and corkscrew comprise a small family of cytoplasmic tyrosine phosphatases that possess two tandem SH2 domains. To investigate the biological functions of Shp-2, a targeted mutation has...
Holland, S J, Gale, N W, Gish, G D, Roth, R A, Songyang, Z, Cantley, L C, ...
Eph-related receptor tyrosine kinases have been implicated in the control of axonal navigation and fasciculation. To investigate the biochemical mechanisms underlying such functions, we have...
Okada, S, Matsuda, M, Anafi, M, Pawson, T, Pessin, J E
Insulin stimulation of Chinese hamster ovary cells expressing the human insulin receptor resulted in a time-dependent decrease in the amount of GTP bound to Rap1. The inactivation of Rap1 was...
The Fps/Fes protein-tyrosine kinase promotes angiogenesis in transgenic mice.
Greer, P, Haigh, J, Mbamalu, G, Khoo, W, Bernstein, A, Pawson, T
The fps/fes proto-oncogene encodes a cytoplasmic protein-tyrosine kinase known to be highly expressed in hematopoietic cells. To investigate fps/fes biological function, an activating mutation was...
Disruption of epithelial gamma delta T cell repertoires by mutation of the Syk tyrosine kinase.
Mallick-Wood, C A, Pao, W, Cheng, A M, Lewis, J M, Kulkarni, S, Bolen, J B, ...
Chimeric mice in which lymphocytes are deficient in the Syk tyrosine kinase have been created. Compared with Syk-positive controls, mice with Syk -/- lymphocytes display substantial depletion of...
O'Bryan, J P, Songyang, Z, Cantley, L, Der, C J, Pawson, T
The Shc adaptor protein, hereafter referred to as ShcA, possesses two distinct phosphotyrosine-recognition modules, a C-terminal Src homology 2 (SH2) domain and an N-terminal phosphotyrosine-binding...
Wiley, S, Gish, G D, Lai, V K, Stephens, R, White, M F, ...
The Shc adaptor protein contains two phosphotyrosine [Tyr(P)]binding modules--an N-terminal Tyr(P) binding (PTB) domain and a C-terminal Src homology 2 (SH2) domain. We have compared the ability of...
Payne, G, Shoelson, S E, Gish, G D, Pawson, T, Walsh, C T
Src homology 2 (SH2) domains are phosphotyrosine-binding modules found within various signal-transducing proteins. We have determined by 125I competition assay and surface plasmon resonance that the...
Kazlauskas, A, Feng, G S, Pawson, T, Valius, M
Ligand-stimulated autophosphorylation of the platelet-derived growth factor receptor (PDGFR) beta subunit creates a number of binding sites for SH2-containing proteins. One of the PDGFR-associated...
Shc proteins are phosphorylated and regulated by the v-Src and v-Fps protein-tyrosine kinases.
McGlade, J, Cheng, A, Pelicci, G, Pelicci, P G, Pawson, T
The mammalian shc gene encodes two overlapping proteins of 46 and 52 kDa, each with a C-terminal Src homology 2 (SH2) domain and an N-terminal glycine/proline-rich sequence, that induce malignant...
Src homology region 2 domains direct protein-protein interactions in signal transduction.
Moran, M F, Koch, C A, Anderson, D, Ellis, C, England, L, Martin, G S, ...
Cytoplasmic proteins that regulate signal transduction or induce cellular transformation, including cytoplasmic protein-tyrosine kinases, p21ras GTPase-activating protein (GAP), phospholipase C...
Liu, X J, Sorisky, A, Zhu, L, Pawson, T
An insulin receptor substrate 1 (IRS-1)-like cDNA was isolated from a Xenopus ovary cDNA library by low-stringency hybridization using rat IRS-1 cDNA as a probe. The deduced amino acid sequence...
A Drosophila shc gene product is implicated in signaling by the DER receptor tyrosine kinase.
Lai, K M, Olivier, J P, Gish, G D, Henkemeyer, M, McGlade, J, Pawson, T
Antibodies to the human Shc adaptor protein were used to isolate a cDNA encoding a Drosophila Shc protein (dShc) by screening an expression library. The dshc gene, which maps to position 67B-C on the...
Aberrant Ras regulation and reduced p190 tyrosine phosphorylation in cells lacking p120-Gap.
Henkemeyer, M, Jacks, T, Pawson, T
The Ras guanine nucleotide-binding protein functions as a molecular switch in signalling downstream of protein-tyrosine kinases. Ras is activated by exchange of GDP for GTP and is turned off by...
Early-passage rat adrenocortical cells were infected with Kirsten murine sarcoma virus and MMCV mouse myc virus, two retroviruses carrying the v-Ki-ras and v-myc oncogenes, respectively. Efficient...
Monoclonal antibodies reactive with either gag or fps portions of the wild-type Fujinami sarcoma virus transforming protein have been used to probe the structure of proteins encoded by mutant genomes...
Weinmaster, G, Hinze, E, Pawson, T
The phosphorylation sites of the P140gag-fps gene product of Fujinami avian sarcoma virus have been identified and localized to different regions of this transforming protein. FSV P140gag-fps...
Ingman-Baker, J, Hinze, E, Levy, J G, Pawson, T
Two monoclonal antibodies have been obtained that recognize antigenic determinants within the C-terminal fps-encoded region of P140gag-fps, the transforming protein of Fujinami avian sarcoma virus...
Structure and phosphorylation of the Fujinami sarcoma virus gene product.
Pawson, T, Kung, T H, Martin, G S
The Fujinami avian sarcoma virus (FSV) transforming gene product, P140, is a fusion protein which contains both gag-related and FSV-specific methionine-containing tryptic peptides. The virion...
Stern, M J, Marengere, L E, Daly, R J, Lowenstein, E J, Kokel, M, Batzer, A, ...
Mutations in the Caenorhabditis elegans gene sem-5 affect cell signaling processes involved in guiding a class of cell migrations and inducing vulval cell fates. The sem-5 sequence encodes a protein...
env Gene of Rous sarcoma virus: identification of the gene product by cell-free translation.
Pawson, T, Mellon, P, Duesberg, P H, Martin, G S
Cell-free translation of polyadenylic acid-selected, denatured virion 70S RNA of the Schmidt-Ruppin strain of Rous sarcoma virus (subgroup A) yields a 64,000-Mr polypeptide which is specifically...
Cell-free translation of avian erythroblastosis virus RNA.
Avian erythroblastosis virus (AEV) RNA rescued from nonproducer cells by superinfection with a helper virus is translated into three polypeptides in the messenger-dependent rabbit reticulocyte...
Cardiac and neurological abnormalities in v-fps transgenic mice.
Yee, S P, Mock, D, Maltby, V, Silver, M, Rossant, J, Bernstein, A, ...
Transgenic mice that widely express the v-fps protein-tyrosine kinase develop several independent pathological conditions, in addition to a high tumor incidence. v-fps expression and protein-tyrosine...
A conserved domain regulates interactions of the v-fps protein-tyrosine kinase with the host cell.
DeClue, J E, Sadowski, I, Martin, G S, Pawson, T
All cytoplasmic protein-tyrosine kinases (PTKs) share a noncatalytic domain, termed SH2, which comprises approximately 100 residues located immediately N-terminal to the kinase domain. A linker in...
Pawson, T, Martin, G S, Smith, A E
Nondefective and transformation-defective virion subunit RNAs from two strains of Rous sarcoma virus (RSV) were translated in cell-free systems derived from Krebs IIA ascites cells, wheat germ, and...
Specific motifs recognized by the SH2 domains of Csk, 3BP2, fps/fes, GRB-2, HCP, SHC, Syk, and Vav.
Songyang, Z, Shoelson, S E, McGlade, J, Olivier, P, Pawson, T, Bustelo, X R, ...
Src homology 2 (SH2) domains provide specificity to intracellular signaling by binding to specific phosphotyrosine (phospho-Tyr)-containing sequences. We recently developed a technique using a...
The Fps/Fes protein-tyrosine kinase promotes angiogenesis in transgenic mice.
Greer, P, Haigh, J, Mbamalu, G, Khoo, W, Bernstein, A, Pawson, T
The fps/fes proto-oncogene encodes a cytoplasmic protein-tyrosine kinase known to be highly expressed in hematopoietic cells. To investigate fps/fes biological function, an activating mutation was...
Panayotou, G, Gish, G, End, P, Truong, O, Gout, I, Dhand, R, ...
The interaction between SH2 domains and phosphotyrosine-containing sequences was examined by real-time measurements of kinetic parameters. The SH2 domains of the p85 subunit of the...
Moran, M F, Polakis, P, McCormick, F, Pawson, T, Ellis, C
The p21ras GTPase-activating protein (GAP) down-regulates p21ras by stimulating its intrinsic GTPase activity. GAP is found predominantly as a monomer in the cytosol of normal cells. However, in...
Sultzman, L, Ellis, C, Lin, L L, Pawson, T, Knopf, J
Upon binding to its cell surface receptor, platelet-derived growth factor (PDGF) causes the tyrosine phosphorylation of phospholipase C-gamma 1 (PLC-gamma 1) and stimulates the production of...
Characterization of elk, a brain-specific receptor tyrosine kinase.
Lhoták, V, Greer, P, Letwin, K, Pawson, T
The elk gene encodes a novel receptorlike protein-tyrosine kinase, which belongs to the eph subfamily. We have previously identified a partial cDNA encompassing the elk catalytic domain (K. Letwin,...
GTPase-activating protein (GAP) stimulates the ability of p21ras to hydrolyze GTP to GDP. Since GAP is phosphorylated by a variety of activated or oncogenic protein-tyrosine kinases, it may couple...
Rottapel, R, Reedijk, M, Williams, D E, Lyman, S D, Anderson, D M, Pawson, T, ...
The W/c-kit and Steel loci respectively encode a receptor tyrosine kinase (Kit) and its extracellular ligand, Steel factor, which are essential for the development of hematopoietic, melanocyte, and...
The v-Src SH3 domain binds phosphatidylinositol 3'-kinase.
Liu, X, Marengere, L E, Koch, C A, Pawson, T
Fibroblasts transformed by v-src or by related oncogenes encoding activated tyrosine kinases contain elevated levels of polyphosphoinositides with phosphate at the D-3 position of the inositol ring,...
Suen, K L, Bustelo, X R, Pawson, T, Barbacid, M
We report the isolation and molecular characterization of the mouse grb2 gene. The product of this gene, the Grb2 protein, is highly related to the Caenorhabditis elegans sem-5 gene product and the...
Muller, A J, Pendergast, A M, Havlik, M H, Puil, L, Pawson, T, Witte, O N
SH2 (src homology region 2) domains are implicated in protein-protein interactions involved in signal transduction pathways. Isolated SH2 domains bind proteins that are tyrosine phosphorylated. A...
Mutational activation of c-raf-1 and definition of the minimal transforming sequence.
Heidecker, G, Huleihel, M, Cleveland, J L, Kolch, W, Beck, T W, Lloyd, P, ...
A series of wild-type and mutant raf genes was transfected into NIH 3T3 cells and analyzed for transforming activity. Full-length wild-type c-raf did not show transforming activity. Two types of...
Myeloid expression of the human c-fps/fes proto-oncogene in transgenic mice.
Greer, P, Maltby, V, Rossant, J, Bernstein, A, Pawson, T
The mammalian c-fps/fes proto-oncogene encodes a 92-kilodalton cytoplasmic protein-tyrosine kinase (p92c-fes), which is expressed in immature and differentiated hematopoietic cells of the myeloid...
Reedijk, M, Liu, X Q, Pawson, T
The interactions of the macrophage colony-stimulating factor 1 (CSF-1) receptor with potential targets were investigated after ligand stimulation either of mouse macrophages or of fibroblasts that...
Lavigueur, A, Maltby, V, Mock, D, Rossant, J, Pawson, T, Bernstein, A
We have investigated the role of the p53 gene in oncogenesis in vivo by generating transgenic mice carrying murine p53 genomic fragments isolated from a mouse Friend erythroleukemia cell line or...
Koch, C A, Moran, M, Sadowski, I, Pawson, T
A conserved noncatalytic domain SH2 (for src homology region 2) is located immediately N terminal to the kinase domains of all cytoplasmic protein-tyrosine kinases. We found that the wild-type v-fps...
Brooks-Wilson, A R, Ball, E, Pawson, T
The P130gag-fps protein-tyrosine kinase of Fujinami sarcoma virus contains an N-terminal fps-specific domain (Nfps) that is important for oncogenicity. The N-terminal 14 amino acids of p60v-src,...
Greer, P A, Meckling-Hansen, K, Pawson, T
A 13-kilobase EcoRI genomic restriction fragment containing the human c-fps/fes proto-oncogene locus was expressed transiently in Cos-1 monkey cells and stably in Rat-2 fibroblasts. In both cases,...
Edwards, A M, Arquint, M, Braun, P E, Roder, J C, Dunn, R J, Pawson, T, ...
Myelin-associated glycoprotein (MAG) has been implicated in the mediation of interactions between oligodendrocytes and neurons during the development of the myelin sheath. Here we show that MAG is...
Lymphoid and mesenchymal tumors in transgenic mice expressing the v-fps protein-tyrosine kinase.
Yee, S P, Mock, D, Greer, P, Maltby, V, Rossant, J, Bernstein, A, ...
src, abl, and fps/fes are prototypes for a family of genes encoding nonreceptor protein-tyrosine kinases. The oncogenic potential of the v-fps protein-tyrosine kinase was investigated by introduction...
Pawson, T, Letwin, K, Lee, T, Hao, Q L, Heisterkamp, N, Groffen, J
We have recently isolated human and rat cDNAs (designated FER and flk, respectively) which encode nonreceptor protein-tyrosine kinases which are very similar to one another and related in sequence...
Multiple cDNAs encoding the esk kinase predict transmembrane and intracellular enzyme isoforms.
Douville, E M, Afar, D E, Howell, B W, Letwin, K, Tannock, L, Ben-David, Y, ...
A novel protein kinase, the Esk kinase, has been isolated from an embryonal carcinoma (EC) cell line by using an expression cloning strategy. Sequence analysis of two independent cDNA clones (2.97...
Caron, L, Abraham, N, Pawson, T, Veillette, A
To understand the mechanism(s) by which p56lck participates in T-cell receptor (TCR) signalling, we have examined the effects of mutations in known regulatory domains of p56lck on the ability of F505...
Eph, Elk, and Eck are prototypes of a large family of transmembrane protein-tyrosine kinases, which are characterized by a highly conserved cysteine-rich domain and two fibronectin type III repeats...
Regulation of a ras-related protein during development of Dictyostelium discoideum.
Pawson, T, Amiel, T, Hinze, E, Auersperg, N, Neave, N, Sobolewski, A, ...
Recent work has shown that DNA sequences related to the mammalian ras proto-oncogenes are highly conserved in eucaryotic evolution. A monoclonal antibody (Y13-259) to mammalian p21ras specifically...
MacDonald, I, Levy, J, Pawson, T
The avian c-fps and mammalian c-fes proto-oncogenes are cognate cellular sequences. Antiserum raised against the P140gag-fps transforming protein of Fujinami avian sarcoma virus specifically...
Sadowski, I, Stone, J C, Pawson, T
Proteins encoded by oncogenes such as v-fps/fes, 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...
MacAuley, A, Auersperg, N, Pawson, T
Rat adrenal cortex cells infected with Kirsten murine sarcoma virus acquire a transformed phenotype in a progressive fashion. The expression of the viral p21ras does not appear to correlate with the...
Multiple SH2-mediated interactions in v-src-transformed cells.
Koch, C A, Moran, M F, Anderson, D, Liu, X Q, Mbamalu, G, Pawson, T
The Src homology 2 (SH2) domain is a noncatalytic region which is conserved among a number of signaling and transforming proteins, including cytoplasmic protein-tyrosine kinases and Ras...
Bcr-Abl oncoproteins bind directly to activators of the Ras signalling pathway.
Puil, L, Liu, J, Gish, G, Mbamalu, G, Bowtell, D, Pelicci, P G, ...
The cytosolic 185 and 210 kDa Bcr-Abl protein tyrosine kinases play important roles in the development of Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia (CML) and acute...
Biochemical and genetic analysis of the Drk SH2/SH3 adaptor protein of Drosophila.
Raabe, T, Olivier, J P, Dickson, B, Liu, X, Gish, G D, Pawson, T, ...
The Drk SH3-SH2-SH3 adaptor protein has been genetically identified in a screen for rate-limiting components acting downstream of the Sevenless (Sev) receptor tyrosine kinase in the developing eye of...
Taylor, G R, Reedijk, M, Rothwell, V, Rohrschneider, L, Pawson, T
The receptors for colony stimulating factor-1 (CSF-1), platelet derived growth factor and the c-kit protein tyrosine kinase (PTK) contain within their catalytic domains a stretch of 60-100 residues,...
The N-terminal region of GAP regulates cytoskeletal structure and cell adhesion.
McGlade, J, Brunkhorst, B, Anderson, D, Mbamalu, G, Settleman, J, Dedhar, S, ...
Ras GTPase activating protein (GAP) possesses a C-terminal domain that interacts with GTP-bound Ras, and an N-terminal region containing two SH2 domains and an SH3 domain. In addition to its...
Colwill, K, Pawson, T, Andrews, B, Prasad, J, Manley, J L, Bell, J C, ...
Mammalian Clk/Sty is the prototype for a family of dual specificity kinases (termed LAMMER kinases) that have been conserved in evolution, but whose physiological substrates are unknown. In a yeast...
Roche, S, McGlade, J, Jones, M, Gish, G D, Pawson, T, Courtneidge, S A
We have investigated the roles of the phosphotyrosine phosphatase Syp (also called SH-PTP2), phospholipase C (PLC) gamma1, rasGTPase Activating Protein (rasGAP) and the adapter molecules Nck and Shc...
Sek4 and Nuk receptors cooperate in guidance of commissural axons and in palate formation.
Orioli, D, Henkemeyer, M, Lemke, G, Klein, R, Pawson, T
Sek4 and Nuk are members of the Eph-related family of receptor protein-tyrosine kinases. These receptors interact with a set of cell surface ligands that have recently been implicated in axon...
HPK1, a hematopoietic protein kinase activating the SAPK/JNK pathway.
Kiefer, F, Tibbles, L A, Anafi, M, Janssen, A, Zanke, B W, Lassam, N, ...
In mammalian cells, a specific stress-activated protein kinase (SAPK/JNK) pathway is activated in response to inflammatory cytokines, injury from heat, chemotherapeutic drugs and UV or ionizing...
Ben-David, Y, Letwin, K, Tannock, L, Bernstein, A, Pawson, T
In a screen of mouse erythroleukemia cDNA expression libraries with anti-phosphotyrosine antibodies, designed to isolate tyrosine kinase coding sequences, we identified several cDNAs encoding...
Signal transduction by normal isoforms and W mutant variants of the Kit receptor tyrosine kinase.
Reith, A D, Ellis, C, Lyman, S D, Anderson, D M, Williams, D E, Bernstein, A, ...
Germline mutations at the Dominant White Spotting (W) and Steel (Sl) loci have provided conclusive genetic evidence that c-kit mediated signal transduction pathways are essential for normal mouse...
The Biomolecular Interaction Network Database and related tools 2005 update
Alfarano, C., Andrade, C. E., Anthony, K., Bahroos, N., Bajec, M., Bantoft, K., ...
The Biomolecular Interaction Network Database (BIND) (http://bind.ca) archives biomolecular interaction, reaction, complex and pathway information. Our aim is to curate the details about molecular...
Margolis, B, Li, N, Koch, A, Mohammadi, M, Hurwitz, D R, Zilberstein, A, ...
Phospholipase C-gamma (PLC-gamma) and GTPase activating protein (GAP) are substrates of EGF, PDGF and other growth factor receptors. Since either PLC-gamma or GAP also bind to the activated receptors...
Meckling-Hansen, K, Nelson, R, Branton, P, Pawson, T
Site-directed mutagenesis of the Fujinami sarcoma virus (FSV) genome has suggested that Tyr 1073 of the P130gag--fps protein-tyrosine kinase is a regulatory site. To investigate directly the ability...
Reedijk, M, Liu, X, Letwin, K, Waterfield, M D, Hunter, T, ...
Efficient binding of active phosphatidylinositol (PI) 3'-kinase to the autophosphorylated macrophage colony stimulating factor receptor (CSF-1R) requires the noncatalytic kinase insert (KI) region of...
Letwin, K, Mizzen, L, Motro, B, Ben-David, Y, Bernstein, A, Pawson, T
Screening of mouse cDNA expression libraries with antibodies to phosphotyrosine resulted in repeated isolation of cDNAs that encode a novel mammalian protein kinase of 774 amino acids, termed Nek1....
A lysine in the ATP-binding site of P130gag-fps is essential for protein-tyrosine kinase activity.
Weinmaster, G, Zoller, M J, Pawson, T
The P130gag-fps transforming protein of Fujinami sarcoma virus (FSV) possesses tyrosine-specific protein kinase activity and autophosphorylates at Tyr-1073. Within the kinase domain of P130gag-fps is...
Migliaccio, E, Mele, S, Salcini, A E, Pelicci, G, Lai, K M, Superti-Furga, G, ...
Shc proteins are targets of activated tyrosine kinases and are implicated in the transmission of activation signals to Ras. The p46shc and p52shc isoforms share a C-terminal SH2 domain, a proline-...
Abnormal mesoderm patterning in mouse embryos mutant for the SH2 tyrosine phosphatase Shp-2.
Saxton, T M, Henkemeyer, M, Gasca, S, Shen, R, Rossi, D J, Shalaby, F, ...
Shp-1, Shp-2 and corkscrew comprise a small family of cytoplasmic tyrosine phosphatases that possess two tandem SH2 domains. To investigate the biological functions of Shp-2, a targeted mutation has...
Holland, S J, Gale, N W, Gish, G D, Roth, R A, Songyang, Z, Cantley, L C, ...
Eph-related receptor tyrosine kinases have been implicated in the control of axonal navigation and fasciculation. To investigate the biochemical mechanisms underlying such functions, we have...
Okada, S, Matsuda, M, Anafi, M, Pawson, T, Pessin, J E
Insulin stimulation of Chinese hamster ovary cells expressing the human insulin receptor resulted in a time-dependent decrease in the amount of GTP bound to Rap1. The inactivation of Rap1 was...
Rivera, G. M., Antoku, S., Gelkop, S., Shin, N. Y., Hanks, S. K., Pawson, T., ...
The Nck family of Src homology (SH) 2/SH3 domain adaptors functions to link tyrosine phosphorylation induced by extracellular signals with downstream regulators of actin dynamics. We investigated the...
Chang, Q, Jorgensen, C, Pawson, T, Hedley, D W
Eph receptors constitute the largest family of receptor tyrosine kinases in the human genome. EphA2 is one prominent member that is overexpressed and functionally altered in many invasive cancers,...