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Signal
Transduction 
Our laboratory uses genetic and biochemical approaches to study the signal
transduction pathways used by hormone and growth fac-tor receptors in
regulating cell growth. Our recent focus is on receptor regulation of
the GTPase family of proteins that control the organization of the actin
cytoskeleton. Dynamic changes in the actin cytoskeleton play a critical
role in cell growth and differentiation, and we have determined that these
dynamic changes are regulated by a complex interplay between adhesion
molecules of the integrin receptor family, members of the Rho family of
GTPases, and plasma membrane ion exchangers. Most interesting is the novel
observation that the link between adhesion receptors and cytoskeletal
organization requires selective members of the family of plasma membrane
Na-H ion exchangers. We found that Na-H exchangers are structurally linked
to the actin cytoskeleton through their direct association with ERM proteins
of the protein 4.1 superfamily of actin-binding proteins. Hence, plasma
membrane ion exchangers can link the actin network to the plasma membrane
and thereby convey input from adhesion molecules and GTPase signaling
networks to the output of cytoskeletal reorganization. The functional
significance of this interplay between integrin receptors, Rho family
GTPases, and plasma membrane ion exchangers in cell contractility, migration,
and proliferation is currently being investigated.
Selected Publications:
Hooley, R, Yu, CY, Symons, M, and Barber, DL G13 stimulates Na-H exchange
through distinct Cdc42-dependent and Rho-dependent pathways. J. Biol.
Chem. 271 (1996): 6152-6158.
Tominaga, T, and Barber, DL. Na-H exchange acts downstream of RhoA to
regulate integrin- induced cell adhesion and spreading. Mol. Biol. Cell
9 (1998): 2287- 2303.
Tominaga, T, Ishizaki, T, Narumiya, S, and Barber, DL. p160ROCK mediates
RhoA activation of Na-H exchange. EMBO J. 17 (1998): 4712-4722
Contact Information:
Email: barber@itsa.ucsf.edu
Phone: (415) 476-3764
Address: Box 0512, Room HSW 604
The University of California, San Francisco, CA 94143, (415) 476-9000
Copyright 2003, The Regents of the University of California.
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