Receptor protein-tyrosine phosphatase α regulates focal adhesion kinase phosphorylation and ErbB2 oncoprotein-mediated mammary epithelial cell motility.
We investigated the role of protein-tyrosine phosphatase α (PTPα) in regulating signaling by the ErbB2 oncoprotein in mammary epithelial cells. Using this model, we demonstrated that activation of ErbB2 led to the transient inactivation of PTPα, suggesting that attenuation of PTPα activity may contribute to enhanced ErbB2 signaling. Furthermore, RNAi-induced suppression of PTPα led to increased cell migration in an ErbB2-dependent manner. The ability of ErbB2 to increase cell motility in the absence of PTPα was characterized by prolonged interaction of GRB7 with ErbB2 and increased association of ErbB2 with a β1-integrin-rich complex, which depended on GRB7-SH2 domain interactions. Finally, suppression of PTPα resulted in increased phosphorylation of focal adhesion kinase on Tyr-407, which induced the recruitment of vinculin and the formation of a novel focal adhesion kinase complex in response to ErbB2 activation in mammary epithelial cells. Collectively, these results reveal a new role for PTPα in the regulation of motility of mammary epithelial cells in response to ErbB2 activation.
From the Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724.
Benoit
B
Boivin
Fauzia
F
Chaudhary
Bryan C
BC
Dickinson
Aftabul
A
Haque
Stephanie C
SC
Pero
Christopher J
CJ
Chang
Nicholas K
NK
Tonks
D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology*; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D042361:Mammary Glands, Human / Q000166:cytology / Q000201:enzymology*; D010766:Phosphorylation / Q000502:physiology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D016596:Vinculin / Q000235:genetics / Q000378:metabolism
D051417:Focal Adhesion Kinase 1; D018719:Erb-b2 Receptor Tyrosine Kinases; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4; D016596:Vinculin; C488955:VCL protein, human; C508053:ERBB2 protein, human; C496050:PTK2 protein, human; C516841:PTPRA protein, human
Breast Cancer; Cell Motility; Dephosphorylation; ErbB2; FAK; Oncogene; PTPα; Phosphatase; Phosphorylation; Protein Kinases