The Anchoring Protein RACK1 Links Protein Kinase Cε to Integrin β Chains
Open Access
- 1 June 2002
- journal article
- Published by Elsevier BV
- Vol. 277 (24), 22073-22084
- https://doi.org/10.1074/jbc.m111644200
Abstract
Integrin affinity is modulated by intracellular signaling cascades, in a process known as “inside-out” signaling, leading to changes in cell adhesion and motility. Protein kinase C (PKC) plays a critical role in integrin-mediated events; however, the mechanism that links PKC to integrins remains unclear. Here, we report that PKCε positively regulates integrin-dependent adhesion, spreading, and motility of human glioma cells. PKCε activation was associated with increased focal adhesion and lamellipodia formation as well as clustering of select integrins, and it is required for phorbol 12-myristate 13-acetate-induced adhesion and motility. We provide novel evidence that the scaffolding protein RACK1 mediates the interaction between integrin β chain and activated PKCε. Both depletion of RACK1 by antisense strategy and overexpression of a truncated form of RACK1 which lacks the integrin binding region resulted in decreased PKCε-induced adhesion and migration, suggesting that RACK1 links PKCε to integrin β chains. Altogether, these results provide a novel mechanistic link between PKC activation and integrin-mediated adhesion and motility.Keywords
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