Kevan M. Shokat, PhD

Kevan M. Shokat, PhD

Professor and Chair, Department of Cellular and Molecular Pharmacology, UCSF; Professor, Department of Chemistry, UC Berkeley; Investigator, Howard Hughes Medical Institute

Phone: (415) 514-0472 (voice)
Box 2280, UCSF
San Francisco, CA 94143-2280

View on UCSF Profiles

Cancer Center Membership

Program Member » Developmental Therapeutics» Cancer Genetics

Research Summary

Research in my laboratory is focused on the discovery of new chemical based tools to decipher cellular signaling networks with an emphasis on protein kinases and more recently, GTPases. The analysis of signal transduction pathways has proven challenging using the traditional tools of biochemistry, genetics, and chemistry. Biochemical approaches are often limited in utility because signaling networks span from the cell surface to the control of transcription and translation, confounding reconstitution efforts from purified proteins. Genetic approaches allow specific perturbation of single components in an intact cell or organism, yet are often confounded by the emergent properties of signaling cascades. Chemical and pharmacological approaches enable rapid, reversible, and graded (dose-dependent) inactivation of single components in intact cells or organisms. Unfortunately, highly selective chemical probes (agonists, antagonists, traceable substrates, etc.) of protein kinases are difficult to develop because the 500 protein kinases share highly homologous ATP binding pockets. My laboratory has solved this fundamental problem for the largest family of enzymes in the human genome, protein kinases, by development of a strategy based on a combination of protein engineering and organic synthesis. We have termed this approach chemical genetics.


Reed College (Portland, Oregon), B.A., 1986, Chemistry
UC Berkeley (Berkeley, California), Ph.D., 1991, Organic Chemistry

Professional Experience

  • 1986-1991
    (Advisor: Prof. Peter G. Schultz, UC Berkeley): Design and synthesis of haptens for the generation of catalytic antibodies. Thesis Title: New Routes to Catalytic Antibodies.
  • 1992-1994
    (Advisor: Prof. Christopher C. Goodnow, Stanford University): Investigation of mechanisms of immune self-tolerance in transgenic mice.
  • 1994-1998
    Assistant Professor of Chemistry and Molecular Biology, Princeton University
  • 1998-1999
    Associate Professor of Chemistry and Molecular Biology, Princeton University
  • 1999-2002
    Associate Professor of Cellular and Molecular Pharmacology, University of California, San Francisco
  • 1999-2002
    Associate Professor of Chemistry, University of California, Berkeley
  • 2001-present
    Professor of Cellular and Molecular Pharmacology, University of California, San Francisco
  • 2002-present
    Professor of Chemistry, University of California, Berkeley
  • 2004-present
    Vice-Chairman of Cellular and Molecular Pharmacology, UCSF
  • 2004-present
    Investigator, Howard Hughes Medical Institute

Honors & Awards

  • 1986
    Phi Beta Kappa - Reed College
  • 1986-1987
    UC Berkeley Regents Fellowship
  • 1989-1990
    UC Berkeley University Fellowship
  • 1992-1994
    Life Sciences Research Foundation Postdoctoral Fellow
  • 1995-1997
    NSF Early Career Development Award
  • 1996-2000
    Pew Scholar in the Biomedical Sciences
  • 1997-1998
    Glaxo-Wellcome Scholar in Organic Chemistry
  • 1997-2000
    Searle Scholar
  • 1997-2000
    Cottrell Scholar
  • 1999-2001
    Alfred P. Sloan Research Fellow
  • 2001
    Protein Society Young Investigator Award
  • 2002
    Eli Lilly Award in Biological Chemistry

Selected Publications

  1. Costa HA, Leitner MG, Sos ML, Mavrantoni A, Rychkova A, Johnson JR, Newton BW, Yee MC, De La Vega FM, Ford JM, Krogan NJ, Shokat KM, Oliver D, Halaszovich CR, Bustamante CD. Discovery and functional characterization of a neomorphic PTEN mutation. Proc Natl Acad Sci U S A. 2015 Oct 26.
    View on PubMed
  2. Schaffer BE, Levin RS, Hertz NT, Maures TJ, Schoof ML, Hollstein PE, Benayoun BA, Banko MR, Shaw RJ, Shokat KM, Brunet A. Identification of AMPK Phosphorylation Sites Reveals a Network of Proteins Involved in Cell Invasion and Facilitates Large-Scale Substrate Prediction. Cell Metab. 2015 Nov 3; 22(5):907-21.
    View on PubMed
  3. Manz BN, Tan YX, Courtney AH, Rutaganira F, Palmer E, Shokat KM, Weiss A. Small molecule inhibition of Csk alters affinity recognition by T cells. Elife. 2015; 4.
    View on PubMed
  4. Lazarus MB, Shokat KM. Discovery and structure of a new inhibitor scaffold of the autophagy initiating kinase ULK1. Bioorg Med Chem. 2015 Sep 1; 23(17):5483-8.
    View on PubMed
  5. Lipp JJ, Marvin MC, Shokat KM, Guthrie C. SR protein kinases promote splicing of nonconsensus introns. Nat Struct Mol Biol. 2015 Aug; 22(8):611-7.
    View on PubMed
  6. Friedel P, Kahle KT, Zhang J, Hertz N, Pisella LI, Buhler E, Schaller F, Duan J, Khanna AR, Bishop PN, Shokat KM, Medina I. WNK1-regulated inhibitory phosphorylation of the KCC2 cotransporter maintains the depolarizing action of GABA in immature neurons. Sci Signal. 2015; 8(383):ra65.
    View on PubMed
  7. Mendez AS, Alfaro J, Morales-Soto MA, Dar AC, McCullagh E, Gotthardt K, Li H, Acosta-Alvear D, Sidrauski C, Korennykh AV, Bernales S, Shokat KM, Walter P. Endoplasmic reticulum stress-independent activation of unfolded protein response kinases by a small molecule ATP-mimic. Elife. 2015; 4.
    View on PubMed
  8. Cage TA, Chanthery Y, Chesler L, Grimmer M, Knight Z, Shokat K, Weiss WA, Gustafson WC. Downregulation of MYCN through PI3K Inhibition in Mouse Models of Pediatric Neural Cancer. Front Oncol. 2015; 5:111.
    View on PubMed
  9. Martin H, Shales M, Fernandez-Piñar P, Wei P, Molina M, Fiedler D, Shokat KM, Beltrao P, Lim W, Krogan NJ. Differential genetic interactions of yeast stress response MAPK pathways. Mol Syst Biol. 2015; 11(4):800.
    View on PubMed
  10. Bailey FP, Byrne DP, Oruganty K, Eyers CE, Novotny CJ, Shokat KM, Kannan N, Eyers PA. The Tribbles 2 (TRB2) pseudokinase binds to ATP and autophosphorylates in a metal-independent manner. Biochem J. 2015 Apr 1; 467(1):47-62.
    View on PubMed
  11. Lazarus MB, Novotny CJ, Shokat KM. Structure of the Human Autophagy Initiating Kinase ULK1 in Complex with Potent Inhibitors. ACS Chem Biol. 2015 Jan 16; 10(1):257-61.
    View on PubMed
  12. Warkentin AA, Lopez MS, Lasater EA, Lin K, He BL, Leung AY, Smith CC, Shah NP, Shokat KM. Overcoming myelosuppression due to synthetic lethal toxicity for FLT3-targeted acute myeloid leukemia therapy. Elife. 2014; 3.
    View on PubMed
  13. Li N, Maly DJ, Chanthery YH, Sirkis DW, Nakamura JL, Berger MS, James CD, Shokat KM, Weiss WA, Persson AI. Radiotherapy followed by aurora kinase inhibition targets tumor-propagating cells in human glioblastoma. Mol Cancer Ther. 2015 Feb; 14(2):419-28.
    View on PubMed
  14. Reed DE, Shokat KM. Targeting osteosarcoma. Proc Natl Acad Sci U S A. 2014 Dec 23; 111(51):18100-1.
    View on PubMed
  15. Martins MM, Zhou AY, Corella A, Horiuchi D, Yau C, Rakshandehroo T, Gordan JD, Levin RS, Johnson J, Jascur J, Shales M, Sorrentino A, Cheah J, Clemons PA, Shamji AF, Schreiber SL, Krogan NJ, Shokat KM, McCormick F, Goga A, Bandyopadhyay S. Linking Tumor Mutations to Drug Responses via a Quantitative Chemical-Genetic Interaction Map. Cancer Discov. 2015 Feb; 5(2):154-67.
    View on PubMed
  16. Ultanir SK, Yadav S, Hertz NT, Oses-Prieto JA, Claxton S, Burlingame AL, Shokat KM, Jan LY, Jan YN. MST3 Kinase Phosphorylates TAO1/2 to Enable Myosin Va Function in Promoting Spine Synapse Development. Neuron. 2014 Dec 3; 84(5):968-82.
    View on PubMed
  17. Crews C, Hertweck C, Shokat K, Suga H, Kostic M. Reflecting on the past and looking forward to the future of bridging chemistry and biology. Chem Biol. 2014 Sep 18; 21(9):1035-6.
    View on PubMed
  18. Chorba JS, Shokat KM. The proprotein convertase subtilisin/kexin type 9 (PCSK9) active site and cleavage sequence differentially regulate protein secretion from proteolysis. J Biol Chem. 2014 Oct 17; 289(42):29030-43.
    View on PubMed
  19. Gustafson WC, Meyerowitz JG, Nekritz EA, Chen J, Benes C, Charron E, Simonds EF, Seeger R, Matthay KK, Hertz NT, Eilers M, Shokat KM, Weiss WA. Drugging MYCN through an allosteric transition in Aurora kinase A. Cancer Cell. 2014 Sep 8; 26(3):414-27.
    View on PubMed
  20. Mantilla CB, Stowe JM, Sieck DC, Ermilov LG, Greising SM, Zhang C, Shokat KM, Sieck GC. TrkB kinase activity maintains synaptic function and structural integrity at adult neuromuscular junctions. J Appl Physiol (1985). 2014 Oct 15; 117(8):910-20.
    View on PubMed

Go to UCSF Profiles, powered by CTSI