Pyk2- and Src-dependent tyrosine phosphorylation of PDK1 regulates focal adhesions.

Article Details

Citation

Taniyama Y, Weber DS, Rocic P, Hilenski L, Akers ML, Park J, Hemmings BA, Alexander RW, Griendling KK

Pyk2- and Src-dependent tyrosine phosphorylation of PDK1 regulates focal adhesions.

Mol Cell Biol. 2003 Nov;23(22):8019-29.

PubMed ID
14585963 [ View in PubMed
]
Abstract

3-Phosphoinositide-dependent protein kinase 1 (PDK1) is a signal integrator that activates the AGC superfamily of serine/threonine kinases. PDK1 is phosphorylated on tyrosine by oxidants, although its regulation by agonists that stimulate G-protein-coupled receptor signaling pathways and the physiological consequences of tyrosine phosphorylation in this setting have not been fully identified. We found that angiotensin II stimulates the tyrosine phosphorylation of PDK1 in vascular smooth muscle in a calcium- and c-Src-dependent manner. The calcium-activated tyrosine kinase Pyk2 acts as a scaffold for Src-dependent phosphorylation of PDK1 on Tyr9, which permits phosphorylation of Tyr373 and -376 by Src. This critical function of Pyk2 is further supported by the observation that Pyk2 and tyrosine-phosphorylated PDK1 colocalize in focal adhesions after angiotensin II stimulation. Importantly, infection of smooth muscle cells with a Tyr9 mutant of PDK1 inhibits angiotensin II-induced tyrosine phosphorylation of paxillin and focal adhesion formation. These observations identify a novel interaction between PDK1 and Pyk2 that regulates the integrity of focal adhesions, which are major compartments for integrating signals for cell growth, apoptosis, and migration.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Proto-oncogene tyrosine-protein kinase SrcP12931Details
Protein-tyrosine kinase 2-betaQ14289Details
3-phosphoinositide-dependent protein kinase 1O15530Details