Role of Src-family kinases in formation of the cortical actin cap at the dorsal cell surface

Exp Cell Res. 2008 Jun 10;314(10):2040-54. doi: 10.1016/j.yexcr.2008.03.018. Epub 2008 Apr 7.

Abstract

Protein-tyrosine phosphorylation is regulated by protein-tyrosine kinases and protein-tyrosine phosphatases (PTPs). Src-family tyrosine kinases (SFKs) participate in the regulation of the actin cytoskeleton. Actin filaments can be accumulated in a cap at the dorsal cell surface, which is called the cortical actin cap. Here, we show that SFKs play an important role in formation of the cortical actin cap. HeLa cells normally exhibit the cortical actin cap, one of the major sites of tyrosine phosphorylation. The cortical actin cap is disrupted by SFK inhibitors or overexpression of the Lyn SH3 domain. Csk-knockout cells form the cortical actin cap when the level of tyrosine phosphorylation is increased by Na(3)VO(4), a PTP inhibitor, and the formation of the cortical actin cap is inhibited by SFK inactivation with re-introduction of Csk. SYF cells lacking SFKs minimally exhibit the cortical actin cap even in the presence of Na(3)VO(4), and transfection with Lyn restores the cortical actin cap in the presence of Na(3)VO(4). Disruption of the cortical actin cap by dominant-negative Cdc42 causes loss of tyrosine phosphorylation at the cell top. These results suggest that SFK(s) is involved in formation of the cortical actin cap, which may serve as a platform of tyrosine phosphorylation signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Animals
  • CSK Tyrosine-Protein Kinase
  • Cell Line
  • Cell Membrane / metabolism*
  • Cell Membrane / ultrastructure
  • Cytoskeleton / metabolism*
  • Cytoskeleton / ultrastructure
  • Humans
  • Mice
  • Mice, Knockout
  • Phosphorylation
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Pyrimidines / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction / physiology
  • Vanadates / metabolism
  • cdc42 GTP-Binding Protein / genetics
  • cdc42 GTP-Binding Protein / metabolism
  • src-Family Kinases / antagonists & inhibitors
  • src-Family Kinases / genetics
  • src-Family Kinases / metabolism*

Substances

  • AG 1879
  • Actins
  • Proto-Oncogene Proteins
  • Pyrimidines
  • Recombinant Fusion Proteins
  • Vanadates
  • Protein-Tyrosine Kinases
  • CSK Tyrosine-Protein Kinase
  • lyn protein-tyrosine kinase
  • src-Family Kinases
  • CSK protein, human
  • cdc42 GTP-Binding Protein