Research Interests

Our group is interested in mechanisms of signal transduction. The ability of a cell to receive signals from the surrounding environment and respond to those signals appropriately is literally a matter of life and death. Whether a cell will proliferate, differentiate, or die, where it will adhere or migrate, virtually all aspects of its behavior depend on the ability to accurately interpret signals. Not only is signaling critical for normal development and the day-to-day function of an organism, but disregulated signaling underlies many human diseases such as cancer and autoimmune disorders. It is now appreciated that one of the central elements of the signaling machinery is the highly regulated and specific formation of protein-protein complexes. The fact that signaling relies on the binding of proteins to each other presents extraordinary opportunities: binding can be used as a means of identifying critical components of signaling pathways, and also provides the basis for strategies to inhibit those pathways in the laboratory or the clinic. We use a combination of biochemical and cell biological techniques to understand signaling pathways such as those that control cell proliferation and the organization of the cytoskeleton. We are also actively pursuing novel proteomic approaches to identify functionally important protein interactions and to characterize interactions on a global scale.

Honors

1985-1988 National Science Foundation Graduate Fellowship

1990-1993 National Institutes of Health Post-Doctoral Fellowship

2000 Raymond and Beverly Sackler endowment award

Selected Publications

Mayer BJ, Hamaguchi M, Hanafusa H. A novel viral oncogene product with structural similarity to phospholipase C. Nature 1988; 332:272-275.

Mayer BJ and Hanafusa H. Association of the v-crk oncogene product with phosphotyrosine-containing proteins and protein kinase activity. Proc Natl Acad Sci USA 1990; 87:2638-2642.

Mayer BJ and Hanafusa H. Mutagenic analysis of the v-crk oncogene: Requirement for SH2 and SH3 domains and correlation between increased cellular phosphotyrosine and transformation. J Virol 1990; 64:3581-3589.

Mayer BJ, Jackson PK, Baltimore D. The noncatalytic Src homology region 2 segment of abl tyrosine kinase binds to tyrosine-phosphorylated cellular proteins with high affinity. Proc Natl Acad Sci USA 1991; 88:627-631.

Mayer BJ, Jackson PK, Van Etten RA, Baltimore D. Point mutations in the abl SH2 domain coordinately impair phosphotyrosine binding in vitro and transforming activity in vivo. Mol Cell Biol 1992; 12:609-618.

Overduin M, Rios CB, Mayer BJ, Baltimore D, Cowburn D. Three dimensional solution structure of the Src homology 2 domain of c-Abl. Cell 1992; 70:697-704.

Cicchetti P, Mayer BJ, Thiel G, Baltimore D. Identification of a protein that binds to the SH3 region of Abl and has homology to Bcr and GAP-rho. Science 1992; 257:803-806

Ren R*, Mayer BJ*, Cicchetti P, Baltimore D. Identification of a 10-amino acid proline-rich SH3 binding site. Science 1993; 259:1157-1161. (*equal contribution)

Mayer BJ, Ren R, Clark KL, Baltimore D. A putative modular domain present in diverse signaling proteins [letter to the editor]. Cell 1993; 73:629-630.

Mayer BJ and Baltimore D. Mutagenic analysis of the roles of SH2 and SH3 domains in regulation of the Abl tyrosine kinase. Mol Cell Biol 1994; 14:2883-2894.

Songyang Z, Carraway K III, Eck MJ, Harrison SC, Feldman RA, Mohammodi M, Schlessinger J, Hubbard S, Smith DP, Eng C, Lorenzo MJ, Ponder BAJ, Mayer BJ, Cantley LC. Catalytic site specificities of protein-tyrosine kinases are critical for selective signaling. Nature 1995; 373:536-539.

Mayer BJ, Hirai H, Sakai R. Evidence that SH2 domains promote processive phosphorylation by protein-tyrosine kinases. Curr Biol 1995; 5:296-305.

Tanaka M, Gupta R, Mayer BJ. Differential inhibition of signaling pathways by dominant-negative SH2/SH3 adaptor proteins. Mol Cell Biol 1995; 15:6829-6837.

Lu W, Katz S, Gupta R, Mayer BJ. Activation of Pak by membrane localization mediated by an SH3 domain from the adaptor protein Nck. Curr Biol 1997; 7:85-94.

Tanaka M, Lu W, Gupta R, Mayer BJ. Expression of mutated Nck SH2/SH3 adaptor respecifies mesodermal cell fate in Xenopus laevis development. Proc Natl Acad Sci USA 1997; 94:4493-4498.

Gupta R and BJ Mayer. Dominant-negative mutants of the SH2/SH3 adapters Nck and Grb2 inhibit MAP kinase activation and mesoderm-specific gene induction by eFGF in Xenopus. Oncogene 1998; 17:2155-65.

Lu W and BJ Mayer. Mechanism of activation of Pak1 kinase by membrane localization. Oncogene 1999; 18:797-806.

Parrini MC and Mayer BJ. Engineering temperature-sensitive SH3 domains. Chem Biol 1999; 6:679-687.

Smith JM, Katz S, Mayer BJ. Activation of the Abl tyrosine kinase in vivo by Src Homology 3 domains from the SH2/SH3 adaptor Nck. J Biol Chem 1999; 274:27956-27962.

Kieran MW, Katz S, Vail B, Zon LI, Mayer BJ. Concentration-dependent positive and negative regulation of a MAP kinase by a MAP kinase kinase. Oncogene 1999; 18:6647-6657.

Lei M, Lu W, Meng W, Parrini MC, Eck MJ, Mayer BJ, Harrison SC. Structure of PAK1 in an autoinhibited conformation reveals a multi-stage activation switch. Cell 2000; 102:387-397.

Adler CE, Aleman LM, Miyoshi-Akiyama T, Tanaka M, Smith JM, Mayer BJ. Abl family kinases and Cbl cooperate with the Nck adaptor to modulate Xenopus development. J Biol Chem 2000; 275:36472-36478.

Xing L, Ge C, Zelter R, Maskevitch G, Mayer BJ, Alexandropoulos K. c-Src signaling induced by the adapters Sin and Cas is mediated by the Rap1 GTPase. Mol Cell Biol 2000; 20:7363-7377.

Escalante M, Courtney J, Chin WG, Teng KK, Kim JI, Fajardo JE, Mayer BJ, Hempstead BL, Birge RB. Phosphorylation of c-Crk II on the negative regulatory Tyr222 mediates nerve growth factor-induced cell spreading and morphogenesis. J Biol Chem 2000; 275:24787-24797.

Chen F, Ma L, Parrini MC, Mao X, Lopez M, Wu C, Marks PW, Davidson L, Kwiatkowski DJ, Kirchhausen T, Orkin SH, Rosen FS, Mayer BJ, Kirschner MW, Alt FW. Cdc42 is required for PIP2-induced actin polymerization and early development but not cell viability. Curr Biol 2000; 10:758-765.

Rohatgi R, Nollau P, Kirschner MW, Mayer BJ. Nck and phosphatidylinositol 4,5-bisphosphate synergistically activate actin polymerization through the N-WASP-ARP2/3 pathway. J Biol Chem 2001; 276: 26448-26452.

Ohba Y, Ikuta K, Ogura A, Matsuda J, Mochizuki N, Nagashima K, Kurokawa K, Mayer BJ, Maki K, Miyazaki J, Matsuda M. Requirement of C3G-dependent Rap1 activation for cell adhesion and embryogenesis. EMBO J 2001; 20:3333-3341.

Miyoshi-Akiyama T, Aleman LM, Smith JM, Adler CE, Mayer BJ. Regulation of Cbl phosphorylation by the Abl tyrosine kinase and the Nck SH2/SH3 adaptor. Oncogene 2001; 20:4058-4069.

Nollau P, Mayer BJ. Profiling the global tyrosine phosphorylation state by Src Homology 2 domain binding. Proc Natl Acad Sci USA 2001; 98: 13531-13536.

Parrini MC, Lei M, Harrison SC, Mayer BJ. Pak1 kinase homodimers are autoinhibited in trans and dissociated upon activation by Cdc42 and Rac1. Mol Cell 2002; 9:73-83.

Fujiwara K, Poikonen K, Aleman L, Valtavaara M, Saksela K, Mayer BJ. A single-chain antibody / epitope system for functional analysis of protein-protein interactions. Biochemistry 2002; 41:12729-12738.

Sharma A, Antoku S, Fujiwara K, Mayer BJ. Functional Interaction Trap: A strategy for validating the functional consequences of tyrosine phosphorylation of specific substrates in vivo. Mol Cell Proteomics 2003; 2:1217-1224.

Rivera GM, Briceño CA, Takeshima F, Snapper SB, Mayer BJ. Inducible clustering of membrane-targeted SH3 domains of the adaptor protein Nck triggers localized actin polymerization. Curr Biol 2004; 14:11-22.

Itoh RE, Kurokawa K, Fujioka A, Sharma A, Mayer BJ and Matsuda M. A FRET-based probe for epidermal growth factor receptor bound non-covalently to a pair of synthetic amphipathic helixes. Exp Cell Res 2005;307:142-152.

Recent Invited Contributions

Mayer BJ. Clamping down on Src activity. Curr Biol 1997; 7:R295-298.

Mayer BJ and Gupta R. Functions of SH2 and SH3 domains. In: Curr Topics Microbiol Immunol. vol 228, Pawson T, ed. Berlin: Springer-Verlag, 1998; 1-22.

Mayer BJ. Protein interactions in signaling cascades. In: Methods in Molecular Biology vol 84, Bar-Sagi D, ed. Totowa, NJ: Humana Press, 1998; 33-48.

Mayer, BJ. Endocytosis: EH domains lend a hand. Curr Biol 1999; 9:R70-73.

Mayer BJ. Using protein-interaction domains to manipulate signaling pathways. In: Signalling networks and cell-cycle control: The molecular basis of cancer and other diseases, Gukind JS, ed. Totowa, NJ: Humana Press, 2000; 439-452.

Mayer BJ. SH3 domains: complexity in moderation. J Cell Sci 2001; 114:1253-1263.

Mayer BJ. Protein-protein interactions [Editorial]. Methods 2001; 24:191-193.

Smith JM and Mayer BJ. Abl: Mechanisms of regulation and activation. Front Biosci 2002; 7:d31-42.

Aasland R, Abrams C, Ampe C, Ball LJ, Bedford MT, Cesareni G, Gimona M, Hurley JH, Jarchau T, Lehto VP, Lemmon MA, Linding R, Mayer BJ, Nagai M, Sudol M, Walter U, Winder SJ. Normalization of nomenclature for peptide motifs as ligands of modular protein domains. FEBS Letts 2002; 513:141-144.

Machida K, Mayer BJ, Nollau P. Profiling the global tyrosine phosphorylation state. Mol Cell Proteomics 2003; 2:215-233

Mayer, BJ. Downstream signaling pathways—modular interactions. In: Handbook of Cell Signaling, Bradshaw R, Dennis E, eds. San Diego, CA: Academic Press, 2003; 471-474.

Sharma A, Antoku S, Mayer BJ. The Functional Interaction Trap: A novel strategy to study specific protein-protein interactions. In: Methods in Proteome and Protein Analysis (MPSA 2002), Kamp RM, Calvete J, Choli-Papadopoulou T, eds. Berlin: Springer-Verlag, 2004; 165-182.

Machida K and Mayer BJ. The SH2 domain: versatile signaling module and pharmaceutical target. Biochim Biophys Acta Proteins and Proteomics 2005; 1747:1-25.

Mayer BJ and Saksela K. SH3 domains. In: Modular Protein Domains, Cesareni G, Gimona M, Sudol M, Yaffe M, eds. Weinheim, Germany: Wiley-VCH, 2005; 37-58.