| First Author | Sun G | Year | 2012 |
| Journal | Mol Cell Biol | Volume | 32 |
| Issue | 18 | Pages | 3776-89 |
| PubMed ID | 22801373 | Mgi Jnum | J:188792 |
| Mgi Id | MGI:5442237 | Doi | 10.1128/MCB.00214-12 |
| Citation | Sun G, et al. (2012) Protein tyrosine phosphatase alpha phosphotyrosyl-789 binds BCAR3 to position Cas for activation at integrin-mediated focal adhesions. Mol Cell Biol 32(18):3776-89 |
| abstractText | Integrin-mediated focal adhesions connect the extracellular matrix and cytoskeleton to regulate cell responses, such as migration. Protein tyrosine phosphatase alpha (PTPalpha) regulates integrin signaling, focal adhesion formation, and migration, but its roles in these events are incompletely understood. The integrin-proximal action of PTPalpha activates Src family kinases, and subsequent phosphorylation of PTPalpha at Tyr789 acts in an unknown manner to promote migration. PTPalpha-null cells were used in reconstitution assays to distinguish PTPalpha-Tyr789-dependent signaling events. This showed that PTPalpha-Tyr789 regulates the localization of PTPalpha and the scaffolding protein Cas to adhesion sites where Cas interacts with and is phosphorylated by Src to initiate Cas signaling. Linking these events, we identify BCAR3 as a molecular connector of PTPalpha and Cas, with phospho-Tyr789 PTPalpha serving as the first defined cellular ligand for the BCAR3 SH2 domain that recruits BCAR3-Cas to adhesions. Our findings reveal a novel role of PTPalpha in integrin-induced adhesion assembly that enables Src-mediated activation of the pivotal function of Cas in migration. |
