Active-Site Inhibitors of mTOR Target Rapamycin-Resistant Outputs of mTORC1 and mTORC2 (2009)
Morris E. Feldman, Beth Apsel, Aino Uotila, Robbie Loewith, Zachary A. Knight, Davide Ruggero, ...
The mammalian target of rapamycin (mTOR) regulates cell growth and survival by integrating nutrient and hormonal signals. These signaling functions are distributed between at least two distinct mTOR...
Sos, Martin L., Fischer, Stefanie, Ullrich, Roland, Peifer, Martin, Heuckmann, Johannes M., Koker, Mirjam, ...
Sos, Martin L., Fischer, Stefanie, Ullrich, Roland, Peifer, Martin, Heuckmann, Johannes M., Koker, Mirjam, ...
Sos, Martin L., Fischer, Stefanie, Ullrich, Roland, Peifer, Martin, Heuckmann, Johannes M., Koker, Mirjam, ...
Kim, Joanne SM, Lilley, Brendan N, Zhang, Chao, Shokat, Kevan M, Sanes, Joshua R, Zhen, Mei
Abstract Background Neurons assemble into a functional network through a sequence of developmental processes including neuronal polarization and synapse formation. In Caenorhabditis elegans , the...
Human Carbonyl Reductase 1 Is an S-Nitrosoglutathione Reductase (2008)
Bateman, Raynard L., Rauh, Daniel, Tavshanjian, Brandon, Shokat, Kevan M.
Cdc28-Clb5 (CDK-S) and Cdc7-Dbf4 (DDK) collaborate to initiate meiotic recombination in yeast (2008)
Wan, Lihong, Niu, Hengyao, Futcher, Bruce, Zhang, Chao, Shokat, Kevan M., Boulton, Simon J., ...
S-phase cyclin-dependent kinase Cdc28–Clb5 (CDK-S) and Dbf4-dependent kinase Cdc7–Dbf4 (DDK) are highly conserved kinases well known for their roles in the initiation of DNA replication. CDK-S is...
Nuclear HuR accumulation through phosphorylation by Cdk1 (2008)
Kim, Hyeon Ho, Abdelmohsen, Kotb, Lal, Ashish, Pullmann, Rudolf, Yang, Xiaoling, Galban, Stefanie, ...
A predominantly nuclear RNA-binding protein, HuR translocates to the cytoplasm in response to stress and proliferative signals, where it stabilizes or modulates the translation of target mRNAs. Here,...
Suppression of p53-dependent senescence by the JNK signal transduction pathway (2007)
Das, Madhumita, Jiang, Feng, Sluss, Hayla Karen, Zhang, Chao, Shokat, Kevan M., Flavell, Richard A., ...
The JNK signaling pathway is implicated in the regulation of the AP1 transcription factor and cell proliferation. Here, we examine the role of JNK by using conditional and chemical genetic alleles of...
Structure-guided development of affinity probes for tyrosine kinases using chemical genetics (2007)
Blair, Jimmy A., Rauh, Daniel, Kung, Charles, Yun, Cai-Hong, Fan, Qi-Wen, Rode, Haridas, ...
Wei, Feng, Wang, Guo-Du, Zhang, Chao, Shokat, Kevan M, Wang, Huimin, Tsien, Joe Z, ...
Abstract Activity-dependent synaptic plasticity is known to be important in learning and memory, persistent pain and drug addiction. Glutamate NMDA receptor activation stimulates several protein...
An Unbiased Cell Morphology–Based Screen for New, Biologically Active Small Molecules (2005)
Masahiro Tanaka, Raynard Bateman, Daniel Rauh, Eugeni Vaisberg, Shyam Ramachandani, Chao Zhang, ...
An imaging-based screen, followed by structural and functional analysis, led to the discovery of new inhibitors of carbonyl reductase 1, a potential anticancer target.
An Unbiased Cell Morphology–Based Screen for New, Biologically Active Small Molecules (2005)
Masahiro Tanaka, Raynard Bateman, Daniel Rauh, Eugeni Vaisberg, Shyam Ramachandani, Chao Zhang, ...
We have implemented an unbiased cell morphology–based screen to identify small-molecule modulators of cellular processes using the Cytometrix (TM) automated imaging and analysis system. This assay...
mutants and the importance of residue Q50 (2004)
Matthew D. Simon, Ken Sato, Gregory A. Weiss, Kevan M. Shokat
phage display selection of engrailed homeodomain
A phage display selection of engrailed homeodomain mutants and the importance of residue Q50 (2004)
Simon, Matthew D., Sato, Ken, Weiss, Gregory A., Shokat, Kevan M.
Mutants of engrailed homeodomain (HD) that retain DNA-binding activity were isolated using a phage display selection. This selection was used to enrich for active DNA-binding clones from a complex...
Control of landmark events in meiosis by the CDK Cdc28 and the meiosis-specific kinase Ime2 (2003)
Benjamin, Kirsten R., Zhang, Chao, Shokat, Kevan M., Herskowitz, Ira
Meiosis is thought to require the protein kinase Ime2 early for DNA replication and the cyclin-dependent kinase Cdc28 late for chromosome segregation. To elucidate the roles of these kinases, we...
Control of landmark events in meiosis by the CDK Cdc28 and the meiosis-specific kinase Ime2 (2003)
Benjamin, Kirsten R., Zhang, Chao, Shokat, Kevan M., Herskowitz, Ira
Meiosis is thought to require the protein kinase Ime2 early for DNA replication and the cyclin-dependent kinase Cdc28 late for chromosome segregation. To elucidate the roles of these kinases, we...
A kinase sequence database: sequence alignments and family assignment (2002)
Buzko, Oleksandr, Shokat, Kevan M.
Summary: The Kinase Sequence Database (KSD) located at http://kinase.ucsf.edu/ksd contains information on 290 protein kinase families derived by profile-based clustering of the non-redundant list of...
Shah, Kavita, Liu, Yi, Deirmengian, Carl, Shokat, Kevan M.
Protein phosphorylation plays a central role in controlling many diverse signal transduction pathways in all cells. Novel protein kinases are identified at a rapid rate using homology cloning methods...
Carroll, Adam S., Bishop, Anthony C., DeRisi, Joseph L., Shokat, Kevan M., O'Shea, Erin K.
In addition to its well-established role in responding to phosphate starvation, the cyclin-dependent kinase Pho85 has been implicated in a number of other physiological responses of the budding yeast...
Chemical Genetic Analysis of Apg1 Reveals A Non-kinase Role in the Induction of Autophagy
Abeliovich, Hagai, Zhang, Chao, Dunn, William A., Shokat, Kevan M., Klionsky, Daniel J.
Macroautophagy is a catabolic membrane trafficking phenomenon that is observed in all eukaryotic cells in response to various stimuli, such as nitrogen starvation and challenge with specific...
Wang, Huimin, Shimizu, Eiji, Tang, Ya-Ping, Cho, Min, Kyin, Maureen, Zuo, Wenqi, ...
By integrating convergent protein engineering and rational inhibitor design, we have developed an in vivo conditional protein knockout and/or manipulation technology. This method is based on the...
Specific Inhibition of Elm1 Kinase Activity Reveals Functions Required for Early G1 Events
Sreenivasan, Aparna, Bishop, Anthony C., Shokat, Kevan M., Kellogg, Douglas R.
In budding yeast, the Elm1 kinase is required for coordination of cell growth and cell division at G2/M. Elm1 is also required for efficient cytokinesis and for regulation of Swe1, the budding yeast...
Control of landmark events in meiosis by the CDK Cdc28 and the meiosis-specific kinase Ime2
Benjamin, Kirsten R., Zhang, Chao, Shokat, Kevan M., Herskowitz, Ira
Meiosis is thought to require the protein kinase Ime2 early for DNA replication and the cyclin-dependent kinase Cdc28 late for chromosome segregation. To elucidate the roles of these kinases, we...
Liu, Ying, Kung, Charles, Fishburn, James, Ansari, Aseem Z., Shokat, Kevan M., Hahn, Steven
Three cyclin-dependent kinases, CDK7, -8, and -9, are specifically involved in transcription by RNA polymerase II (Pol II) and target the Pol II C-terminal domain (CTD). The role of CDK7 and CDK8...
Provance, D. William, Gourley, Christopher R., Silan, Colleen M., Cameron, L. C., Shokat, Kevan M., Goldenring, James R., ...
Selective, in situ inhibition of individual unconventional myosins is a powerful approach to determine their specific physiological functions. Here, we report the engineering of a myosin Vb mutant...
A phage display selection of engrailed homeodomain mutants and the importance of residue Q50
Simon, Matthew D., Sato, Ken, Weiss, Gregory A., Shokat, Kevan M.
Mutants of engrailed homeodomain (HD) that retain DNA-binding activity were isolated using a phage display selection. This selection was used to enrich for active DNA-binding clones from a complex...
An Unbiased Cell Morphology–Based Screen for New, Biologically Active Small Molecules
Tanaka, Masahiro, Bateman, Raynard, Rauh, Daniel, Vaisberg, Eugeni, Ramachandani, Shyam, Zhang, Chao, ...
We have implemented an unbiased cell morphology–based screen to identify small-molecule modulators of cellular processes using the Cytometrix (TM) automated imaging and analysis system. This assay...
A Chemical-Genetic Strategy Implicates Myosin-1c in Adaptation by Hair Cells
Holt, Jeffrey R., Gillespie, Susan K.H., Provance, D. William, Shah, Kavita, Shokat, Kevan M., Corey, David P., ...
Myosin-1c (also known as myosin-Iβ) has been proposed to mediate the slow component of adaptation by hair cells, the sensory cells of the inner ear. To test this hypothesis, we mutated tyrosine-61...
Specific Inhibition of Elm1 Kinase Activity Reveals Functions Required for Early G1 Events
Sreenivasan, Aparna, Bishop, Anthony C., Shokat, Kevan M., Kellogg, Douglas R.
Combining chemical genetics and proteomics to identify protein kinase substrates
Dephoure, Noah, Howson, Russell W., Blethrow, Justin D., Shokat, Kevan M., O'Shea, Erin K.
Phosphorylation is a ubiquitous protein modification important for regulating nearly every aspect of cellular biology. Protein kinases are highly conserved and constitute one of the largest gene...
Wei, Feng, Wang, Guo-Du, Zhang, Chao, Shokat, Kevan M, Wang, Huimin, Tsien, Joe Z, ...
Activity-dependent synaptic plasticity is known to be important in learning and memory, persistent pain and drug addiction. Glutamate NMDA receptor activation stimulates several protein kinases,...
Shah, Kavita, Liu, Yi, Deirmengian, Carl, Shokat, Kevan M.
Protein phosphorylation plays a central role in controlling many diverse signal transduction pathways in all cells. Novel protein kinases are identified at a rapid rate using homology cloning methods...
Carroll, Adam S., Bishop, Anthony C., DeRisi, Joseph L., Shokat, Kevan M., O'Shea, Erin K.
In addition to its well-established role in responding to phosphate starvation, the cyclin-dependent kinase Pho85 has been implicated in a number of other physiological responses of the budding yeast...
Chemical Genetic Analysis of Apg1 Reveals A Non-kinase Role in the Induction of Autophagy
Abeliovich, Hagai, Zhang, Chao, Dunn, William A., Shokat, Kevan M., Klionsky, Daniel J.
Macroautophagy is a catabolic membrane trafficking phenomenon that is observed in all eukaryotic cells in response to various stimuli, such as nitrogen starvation and challenge with specific...
Wang, Huimin, Shimizu, Eiji, Tang, Ya-Ping, Cho, Min, Kyin, Maureen, Zuo, Wenqi, ...
By integrating convergent protein engineering and rational inhibitor design, we have developed an in vivo conditional protein knockout and/or manipulation technology. This method is based on the...
Specific Inhibition of Elm1 Kinase Activity Reveals Functions Required for Early G1 Events
Sreenivasan, Aparna, Bishop, Anthony C., Shokat, Kevan M., Kellogg, Douglas R.
In budding yeast, the Elm1 kinase is required for coordination of cell growth and cell division at G2/M. Elm1 is also required for efficient cytokinesis and for regulation of Swe1, the budding yeast...
Control of landmark events in meiosis by the CDK Cdc28 and the meiosis-specific kinase Ime2
Benjamin, Kirsten R., Zhang, Chao, Shokat, Kevan M., Herskowitz, Ira
Meiosis is thought to require the protein kinase Ime2 early for DNA replication and the cyclin-dependent kinase Cdc28 late for chromosome segregation. To elucidate the roles of these kinases, we...
Liu, Ying, Kung, Charles, Fishburn, James, Ansari, Aseem Z., Shokat, Kevan M., Hahn, Steven
Three cyclin-dependent kinases, CDK7, -8, and -9, are specifically involved in transcription by RNA polymerase II (Pol II) and target the Pol II C-terminal domain (CTD). The role of CDK7 and CDK8...
Provance, D. William, Gourley, Christopher R., Silan, Colleen M., Cameron, L. C., Shokat, Kevan M., Goldenring, James R., ...
Selective, in situ inhibition of individual unconventional myosins is a powerful approach to determine their specific physiological functions. Here, we report the engineering of a myosin Vb mutant...
A phage display selection of engrailed homeodomain mutants and the importance of residue Q50
Simon, Matthew D., Sato, Ken, Weiss, Gregory A., Shokat, Kevan M.
Mutants of engrailed homeodomain (HD) that retain DNA-binding activity were isolated using a phage display selection. This selection was used to enrich for active DNA-binding clones from a complex...
Chemical genomic profiling to identify intracellular targets of a multiplex kinase inhibitor
Kung, Charles, Kenski, Denise M., Dickerson, Scott H., Howson, Russell W., Kuyper, Lee F., Madhani, Hiten D., ...
The identification of the kinase or kinases targeted by protein kinase inhibitors is a critical challenge in validating their use as therapeutic agents or molecular probes. Here, to address this...
An Unbiased Cell Morphology–Based Screen for New, Biologically Active Small Molecules
Tanaka, Masahiro, Bateman, Raynard, Rauh, Daniel, Vaisberg, Eugeni, Ramachandani, Shyam, Zhang, Chao, ...
We have implemented an unbiased cell morphology–based screen to identify small-molecule modulators of cellular processes using the Cytometrix (TM) automated imaging and analysis system. This assay...
Combining chemical genetics and proteomics to identify protein kinase substrates
Dephoure, Noah, Howson, Russell W., Blethrow, Justin D., Shokat, Kevan M., O'Shea, Erin K.
Phosphorylation is a ubiquitous protein modification important for regulating nearly every aspect of cellular biology. Protein kinases are highly conserved and constitute one of the largest gene...
Specific Inhibition of Elm1 Kinase Activity Reveals Functions Required for Early G1 Events
Sreenivasan, Aparna, Bishop, Anthony C., Shokat, Kevan M., Kellogg, Douglas R.
Wei, Feng, Wang, Guo-Du, Zhang, Chao, Shokat, Kevan M, Wang, Huimin, Tsien, Joe Z, ...
Activity-dependent synaptic plasticity is known to be important in learning and memory, persistent pain and drug addiction. Glutamate NMDA receptor activation stimulates several protein kinases,...
Wan, Lihong, Zhang, Chao, Shokat, Kevan M., Hollingsworth, Nancy M.
Genetic studies in budding yeast have provided many fundamental insights into the specialized cell division of meiosis, including the identification of evolutionarily conserved meiosis-specific genes...
Burkard, Mark E., Randall, Catherine L., Larochelle, Stéphane, Zhang, Chao, Shokat, Kevan M., Fisher, Robert P., ...
Polo-like kinases (Plks) play crucial roles in mitosis and cell division. Whereas lower eukaryotes typically contain a single Plk, mammalian cells express several closely related but functionally...
Chemical inhibition of the TFIIH-associated kinase Cdk7/Kin28 does not impair global mRNA synthesis
Kanin, Elenita I., Kipp, Ryan T., Kung, Charles, Slattery, Matthew, Viale, Agnes, Hahn, Steven, ...
The process of gene transcription requires the recruitment of a hypophosphorylated form of RNA polymerase II (Pol II) to a gene promoter. The TFIIH-associated kinase Cdk7/Kin28 hyperphosphorylates...
Van Keymeulen, Alexandra, Wong, Kit, Knight, Zachary A., Govaerts, Cedric, Hahn, Klaus M., Shokat, Kevan M., ...
Chemoattractants like f-Met-Leu-Phe (fMLP) induce neutrophils to polarize by triggering divergent signals that promote the formation of protrusive filamentous actin (F-actin; frontness) and...
Suppression of p53-dependent senescence by the JNK signal transduction pathway
Das, Madhumita, Jiang, Feng, Sluss, Hayla K., Zhang, Chao, Shokat, Kevan M., Flavell, Richard A., ...
The JNK signaling pathway is implicated in the regulation of the AP1 transcription factor and cell proliferation. Here, we examine the role of JNK by using conditional and chemical genetic alleles of...
Balla, Andras, Kim, Yeun Ju, Varnai, Peter, Szentpetery, Zsofia, Knight, Zachary, Shokat, Kevan M., ...
Type III phosphatidylinositol (PtdIns) 4-kinases (PI4Ks) have been previously shown to support plasma membrane phosphoinositide synthesis during phospholipase C activation and Ca2+ signaling. Here,...
A surface on the androgen receptor that allosterically regulates coactivator binding
Estébanez-Perpiñá, Eva, Arnold, Alexander A., Nguyen, Phuong, Rodrigues, Edson Delgado, Mar, Ellena, Bateman, Raynard, ...
Current approaches to inhibit nuclear receptor (NR) activity target the hormone binding pocket but face limitations. We have proposed that inhibitors, which bind to nuclear receptor surfaces that...
Entry of B Cell Receptor into Signaling Domains Is Inhibited in Tolerant B Cells
Weintraub, Bennett C., Jun, Jesse Eunsuk, Bishop, Anthony C., Shokat, Kevan M., Thomas, Matthew L., Goodnow, Christopher C.
Signal transduction through the B cell antigen receptor (BCR) is altered in B cells that express a receptor that recognizes self-antigen. To understand the molecular basis for the change in signaling...
Sekiya-Kawasaki, Mariko, Groen, Aaron Chris, Kaksonen, Marko, Watson, Hadiya A., Zhang, Chao, ...
We used chemical genetics to control the activity of budding yeast Prk1p, which is a protein kinase that is related to mammalian GAK and AAK1, and which targets several actin regulatory proteins...
Cdc28–Clb5 (CDK-S) and Cdc7–Dbf4 (DDK) collaborate to initiate meiotic recombination in yeast
Wan, Lihong, Niu, Hengyao, Futcher, Bruce, Zhang, Chao, Shokat, Kevan M., Boulton, Simon J., ...
S-phase cyclin-dependent kinase Cdc28–Clb5 (CDK-S) and Dbf4-dependent kinase Cdc7–Dbf4 (DDK) are highly conserved kinases well known for their roles in the initiation of DNA replication. CDK-S is...
Covalent capture of kinase-specific phosphopeptides reveals Cdk1-cyclin B substrates
Blethrow, Justin D., Glavy, Joseph S., Morgan, David O., Shokat, Kevan M.
We describe a method for rapid identification of protein kinase substrates. Cdk1 was engineered to accept an ATP analog that allows it to uniquely label its substrates with a bio-orthogonal phosphate...
Kharas, Michael G., Janes, Matthew R., Scarfone, Vanessa M., Lilly, Michael B., Knight, Zachary A., Shokat, Kevan M., ...
Some cases of pre–B cell acute lymphoblastic leukemia (pre–B-ALL) are caused by the Philadelphia (Ph) chromosome–encoded BCR-ABL oncogene, and these tend to have a poor prognosis. Inhibitors of...
Levin, Susan E., Zhang, Chao, Kadlecek, Theresa A., Shokat, Kevan M., Weiss, Arthur
ZAP-70 is a cytoplasmic protein tyrosine kinase that is required for T cell antigen receptor (TCR) signaling. Both mice and humans deficient in ZAP-70 fail to develop functional T cells, thus...
T cell receptor signaling controls Foxp3 expression via PI3K, Akt, and mTOR
Sauer, Stephan, Bruno, Ludovica, Hertweck, Arnulf, Finlay, David, Leleu, Marion, Spivakov, Mikhail, ...
Regulatory T (Treg) cells safeguard against autoimmunity and immune pathology. Because determinants of the Treg cell fate are not completely understood, we have delineated signaling events that...
Nuclear HuR accumulation through phosphorylation by Cdk1
Kim, Hyeon Ho, Abdelmohsen, Kotb, Lal, Ashish, Pullmann, Rudolf, Yang, Xiaoling, Galban, Stefanie, ...
A predominantly nuclear RNA-binding protein, HuR translocates to the cytoplasm in response to stress and proliferative signals, where it stabilizes or modulates the translation of target mRNAs. Here,...
The Yeast LATS/Ndr Kinase Cbk1 Regulates Growth via Golgi-dependent Glycosylation and Secretion
Kurischko, Cornelia, Kuravi, Venkata K., Wannissorn, Nattha, Nazarov, Pavel A., Husain, Michelle, Zhang, Chao, ...
Saccharomyces cerevisiae Cbk1 is a LATS/Ndr protein kinase and a downstream component of the regulation of Ace2 and morphogenesis (RAM) signaling network. Cbk1 and the RAM network are required for...
Active-Site Inhibitors of mTOR Target Rapamycin-Resistant Outputs of mTORC1 and mTORC2
Feldman, Morris E, Apsel, Beth, Uotila, Aino, Loewith, Robbie, Knight, Zachary A, Ruggero, Davide, ...
The mammalian target of rapamycin (mTOR) regulates cell growth and survival by integrating nutrient and hormonal signals. These signaling functions are distributed between at least two distinct mTOR...
Burkard, Mark E., Maciejowski, John, Rodriguez-Bravo, Verónica, Repka, Michael, Lowery, Drew M., Clauser, Karl R., ...
Self-regulated movement of Polo-like kinase 1 to the midzone of the mitotic spindle initiates a local signaling cascade that activates the cell division machinery at the cell's equator.
Evolution of Phosphoregulation: Comparison of Phosphorylation Patterns across Yeast Species
Beltrao, Pedro, Trinidad, Jonathan C., Fiedler, Dorothea, Roguev, Assen, Lim, Wendell A., Shokat, Kevan M., ...
Analysis of the phosphoproteomes and the gene interaction networks of divergent yeast species defines the relative contribution of changes in protein phosphorylation pathways to the generation of...
Morgan, Daniel J., Weisenhaus, Michael, Shum, Sara, Su, Thomas, Zheng, Ruimao, Zhang, Chao, ...
Studies on cAMP signaling and protein kinase A (PKA) function in vivo are limited by the lack of highly specific inhibitors that can be used in primary cell culture and whole animals. Previously we...
A Complex-based Reconstruction of the Saccharomyces cerevisiae Interactome *S⃞
Wang, Haidong, Kakaradov, Boyko, Collins, Sean R., Karotki, Lena, Fiedler, Dorothea, Shales, Michael, ...
Most cellular processes are performed by proteomic units that interact with each other. These units are often stoichiometrically stable complexes comprised of several proteins. To obtain a faithful...
Wang, Jian, Knight, Zachary A., Fiedler, Dorothea, Williams, Olusegun, Shokat, Kevan M., Pearce, David
The pathways implicated in the control of epithelial Na+ channel (ENaC)-dependent Na+ transport in renal collecting duct cells share substantial parallels with those implicated in insulin-regulated...
Sos, Martin L., Fischer, Stefanie, Ullrich, Roland, Peifer, Martin, Heuckmann, Johannes M., Koker, Mirjam, ...
In cancer, genetically activated proto-oncogenes often induce “upstream” dependency on the activity of the mutant oncoprotein. Therapeutic inhibition of these activated oncoproteins can induce...