|
Faculty
Bruce J. Mayer
Associate Professor of Genetics &
Developmental Biology
bmayer@neuron.uchc.edu
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. |
