Targeting membrane-localized focal adhesion kinase to focal adhesions. Roles of tyrosine phosphorylation and Src family kinases

Ben Zion Katz, Lewis Romer, Shingo Miyamoto, Tova Volberg, Kazue Matsumoto, Edna Cukierman, Benjamin Geiger, Kenneth M. Yamada

Research output: Contribution to journalArticle

Abstract

In the present study, we examined regulation of activated focal adhesion kinase localization in focal adhesions. By using focal adhesion kinase fused to an inert transmembrane anchor, we found that the focal contact targeting region within focal adhesion kinase was preserved in the membrane-targeted fusion protein. However, upon tyrosine phosphorylation, full-length focal adhesion kinase became excluded from focal adhesions. This negative regulation of localization could be abolished by mutating key amino acid residues of focal adhesion kinase shown previously to be involved in adhesion-mediated signal transduction. Hyper-phosphorylation of endogenous focal adhesion kinase induced by pervanadate resulted in a similar reduction of localization at focal adhesions. We also show here that Src family kinases are essential for the phosphorylation-dependent exclusion of focal adhesion kinase from focal adhesions. We propose here a molecular model for the tyrosine phosphorylation-dependent regulation of focal adhesion kinase organization involving Src kinases and an inhibitory phosphorylation of the C-terminal (Tyr-925) tyrosine residue.

Original languageEnglish (US)
Pages (from-to)29115-29120
Number of pages6
JournalJournal of Biological Chemistry
Volume278
Issue number31
DOIs
StatePublished - Aug 1 2003

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Focal Adhesion Protein-Tyrosine Kinases
Phosphorylation
Focal Adhesions
src-Family Kinases
Tyrosine
Adhesion
Membranes
Membrane Fusion Proteins
Signal transduction
Molecular Models
Anchors
Signal Transduction
Fusion reactions
Amino Acids

ASJC Scopus subject areas

  • Biochemistry

Cite this

Targeting membrane-localized focal adhesion kinase to focal adhesions. Roles of tyrosine phosphorylation and Src family kinases. / Katz, Ben Zion; Romer, Lewis; Miyamoto, Shingo; Volberg, Tova; Matsumoto, Kazue; Cukierman, Edna; Geiger, Benjamin; Yamada, Kenneth M.

In: Journal of Biological Chemistry, Vol. 278, No. 31, 01.08.2003, p. 29115-29120.

Research output: Contribution to journalArticle

Katz, Ben Zion ; Romer, Lewis ; Miyamoto, Shingo ; Volberg, Tova ; Matsumoto, Kazue ; Cukierman, Edna ; Geiger, Benjamin ; Yamada, Kenneth M. / Targeting membrane-localized focal adhesion kinase to focal adhesions. Roles of tyrosine phosphorylation and Src family kinases. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 31. pp. 29115-29120.
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AU - Cukierman, Edna

AU - Geiger, Benjamin

AU - Yamada, Kenneth M.

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