Areas of Interest
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.
Lab Rotation Projects
Various projects aimed at profiling tyrosine phosphorylation
in cells and tumor samples; signal transduction via tyrosine
kinases and their substrates; regulation of actin cytoskeleton
by extracellular signals.
Selected Publications
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.
Sharma A, Antoku S, Fujiwara K, Mayer BJ. 2003. Functional
Interaction Trap: A strategy for validating the functional
consequences of tyrosine phosphorylation of specific substrates
in vivo.
Mol Cell Proteomics 2:1217-1224.
Machida K, Mayer BJ, Nollau P. 2003. Profiling the global
tyrosine phosphorylation state.
Mol Cell Proteomics 2:215-233.
Smith JM and Mayer BJ. 2002. Abl: Mechanisms of regulation
and activation.
Front Biosci 7:d31-42.
Fujiwara K, Poikonen K, Aleman L, Valtavaara M, Saksela K,
Mayer BJ. 2002. A single-chain antibody / epitope system for
functional analysis of protein-protein interactions.
Biochemistry 41:12729-12738.
Parrini MC, Lei M, Harrison SC, Mayer BJ. 2002. Pak1 kinase
homodimers are autoinhibited in trans and dissociated upon
activation by Cdc42 and Rac1.
Mol Cell 9: 73-83.
Nollau P, Mayer BJ. 2001. Profiling the global tyrosine
phosphorylation state by Src Homology 2 domain binding.
Proc Natl Acad Sci USA 98: 13531-13536.
Miyoshi-Akiyama T, Aleman LM, Smith JM, Adler CE, Mayer BJ.
2001. Regulation of Cbl phosphorylation by the Abl tyrosine
kinase and the Nck SH2/SH3 adaptor.
Oncogene 20:4058-4069.
Rohatgi R, Nollau P, Kirschner MW, Mayer BJ. 2001. Nck and
phosphatidylinositol 4,5-bisphosphate synergistically activate
actin polymerization through the N-WASP-ARP2/3 pathway.
J Biol Chem 276:26448-26452.
Mayer BJ. 2001. SH3 domains: complexity in moderation.
J Cell Sci 114:1253-1263.
Adler CE, Miyoshi-Akiyama T, Aleman LM, Tanaka M, Smith JM,
Mayer BJ. 2000. Abl family kinases and Cbl cooperate with the
Nck adaptor to modulate Xenopus development.
J Biol Chem 275:36472-36478.
Lei M, Lu W, Meng W, Parrini MC, Eck MJ, Mayer BJ , Harrison
SC. 2000. Structure of PAK1 in an autoinhibited conformation
reveals a multi-stage activation switch.
Cell 102:387-397.
Mayer, BJ. 2000. 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, 439-452.
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