Cortactin is a functional target of E-cadherin-activated Src family kinases in MCF7 epithelial monolayers.
Src family kinases (SFKs) signal in response to E-cadherin to support cadherin adhesion and the integrity of cell-cell contacts (McLachlan, R. W., Kraemer, A., Helwani, F. M., Kovacs, E. M., and Yap, A. S. (2007) Mol. Biol. Cell 18, 3214-3223). We now identify the actin-regulatory protein, cortactin, as a target of E-cadherin-activated SFK signaling. Tyr-phosphorylated cortactin was found at cell-cell contacts in established epithelial monolayers, and cortactin became acutely tyrosine-phosphorylated when E-cadherin adhesion was engaged. In all circumstances, cortactin tyrosine phosphorylation was blocked by inhibiting SFK signaling. Importantly, Tyr-phosphorylated cortactin was necessary to preserve the integrity of cadherin contacts and the perijunctional actin cytoskeleton. Moreover, expression of a phosphomimetic cortactin mutant could prevent SFK blockade from disrupting cadherin organization, thereby placing cortactin functionally downstream of SFK signaling at cadherin adhesions. We conclude that SFK and cortactin constitute an important signaling pathway that functionally links E-cadherin adhesion and the actin cytoskeleton.
Ren
Gang
G
Division of Molecular Cell Biology, Institute for Molecular Bioscience, University of Queensland, St. Lucia, Brisbane 4072, Australia.
Helwani
Falak M
FM
Verma
Suzie
S
McLachlan
Robert W
RW
Weed
Scott A
SA
Yap
Alpha S
AS
D000199:Actins / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D002450:Cell Communication; D045744:Cell Line, Tumor; D051356:Cortactin / Q000378:metabolism / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D010766:Phosphorylation; D014443:Tyrosine / Q000737:chemistry; D019061:src-Family Kinases / Q000378:metabolism*
D000199:Actins; D015820:Cadherins; D051356:Cortactin; D014443:Tyrosine; D019061:src-Family Kinases