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Vol. 9, Issue 7, 1803-1816, July 1998
Department of Anatomy and Cell Biology, Program in Cell and
Molecular Biology, State University of New York Health Science Center
at Syracuse, Syracuse, New York 13210
We have previously shown that the LIM domains of paxillin operate
as the focal adhesion (FA)-targeting motif of this protein. In the
current study, we have identified the capacity of paxillin LIM2 and
LIM3 to serve as binding sites for, and substrates of serine/threonine
kinases. The activities of the LIM2- and LIM3-associated kinases were
stimulated after adhesion of CHO.K1 cells to fibronectin; consequently,
a role for LIM domain phosphorylation in regulating the subcellular
localization of paxillin after adhesion to fibronectin was
investigated. An avian paxillin-CHO.K1 model system was used to explore
the role of paxillin phosphorylation in paxillin localization to FAs.
We found that mutations of paxillin that mimicked LIM domain
phosphorylation accelerated fibronectin-induced localization of
paxillin to focal contacts. Further, blocking phosphorylation of the
LIM domains reduced cell adhesion to fibronectin, whereas constitutive
LIM domain phosphorylation significantly increased the capacity of
cells to adhere to fibronectin. The potentiation of FA targeting and
cell adhesion to fibronectin was specific to LIM domain phosphorylation
as mutation of the amino-terminal tyrosine and serine residues of
paxillin that are phosphorylated in response to fibronectin adhesion
had no effect on the rate of FA localization or cell adhesion. This
represents the first demonstration of the regulation of protein
localization through LIM domain phosphorylation and suggests a novel
mechanism of regulating LIM domain function. Additionally, these
results provide the first evidence that paxillin contributes to
"inside-out" integrin-mediated signal transduction.
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L. Herreros, J. L. Rodriguez-Fernandez, M. C. Brown, J. L. Alonso-Lebrero, C. Cabanas, F. Sanchez-Madrid, N. Longo, C. E. Turner, and P. Sanchez-Mateos Paxillin Localizes to the Lymphocyte Microtubule Organizing Center and Associates with the Microtubule Cytoskeleton J. Biol. Chem., August 18, 2000; 275(34): 26436 - 26440. [Abstract] [Full Text] [PDF]
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S. N. Nikolopoulos and C. E. Turner Integrin-linked Kinase (ILK) Binding to Paxillin LD1 Motif Regulates ILK Localization to Focal Adhesions J. Biol. Chem., June 22, 2001; 276(26): 23499 - 23505. [Abstract] [Full Text] [PDF]
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