Tyrosine phosphorylation of rac1: A role in regulation of cell spreading

Fumin Chang, Christopher Lemmon, Daniel Lietha, Michael Eck, Lewis Romer

Research output: Contribution to journalArticle

Abstract

Rac1 influences a multiplicity of vital cellular- and tissue-level control functions, making it an important candidate for targeted therapeutics. The activity of the Rho family member Cdc42 has been shown to be modulated by tyrosine phosphorylation at position 64. We therefore investigated consequences of the point mutations Y64F and Y64D in Rac1. Both mutations altered cell spreading from baseline in the settings of wild type, constitutively active, or dominant negative Rac1 expression, and were accompanied by differences in Rac1 targeting to focal adhesions. Rac1-Y64F displayed increased GTP-binding, increased association with βPIX, and reduced binding with RhoGDI as compared with wild type Rac1. Rac1-Y64D had less binding to PAK than Rac1-WT or Rac1-64F. In vitro assays demonstrated that Y64 in Rac1 is a target for FAK and Src. Taken together, these data suggest a mechanism for the regulation of Rac1 activity by non-receptor tyrosine kinases, with consequences for membrane extension.

Original languageEnglish (US)
Article numbere28587
JournalPLoS One
Volume6
Issue number12
DOIs
StatePublished - Dec 6 2011

Fingerprint

Phosphorylation
Focal Adhesions
Level control
Guanosine Triphosphate
Point Mutation
Protein-Tyrosine Kinases
Tyrosine
tyrosine
Assays
phosphorylation
Adhesion
Cells
Association reactions
Tissue
Membranes
Mutation
point mutation
adhesion
phosphotransferases (kinases)
cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Tyrosine phosphorylation of rac1 : A role in regulation of cell spreading. / Chang, Fumin; Lemmon, Christopher; Lietha, Daniel; Eck, Michael; Romer, Lewis.

In: PLoS One, Vol. 6, No. 12, e28587, 06.12.2011.

Research output: Contribution to journalArticle

Chang, Fumin ; Lemmon, Christopher ; Lietha, Daniel ; Eck, Michael ; Romer, Lewis. / Tyrosine phosphorylation of rac1 : A role in regulation of cell spreading. In: PLoS One. 2011 ; Vol. 6, No. 12.
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