β-Arrestin1 and Signal-transducing Adaptor Molecule 1 (STAM1) Cooperate to Promote Focal Adhesion Kinase Autophosphorylation and Chemotaxis Via the Chemokine Receptor CXCR4

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2016 Oct 30

PMID 27789711

Citations 24

Authors

Olga Alekhina

Adriano Marchese

Affiliations

Soon will be listed here.

Abstract

The chemokine receptor CXCR4 and its chemokine ligand CXCL12 mediate directed cell migration during organogenesis, immune responses, and metastatic disease. However, the mechanisms governing CXCL12/CXCR4-dependent chemotaxis remain poorly understood. Here, we show that the β-arrestin1·signal-transducing adaptor molecule 1 (STAM1) complex, initially identified to govern lysosomal trafficking of CXCR4, also mediates CXCR4-dependent chemotaxis. Expression of minigene fragments from β-arrestin1 or STAM1, known to disrupt the β-arrestin1·STAM1 complex, and RNAi against β-arrestin1 or STAM1, attenuates CXCL12-induced chemotaxis. The β-arrestin1·STAM1 complex is necessary for promoting autophosphorylation of focal adhesion kinase (FAK). FAK is necessary for CXCL12-induced chemotaxis and associates with and localizes with β-arrestin1 and STAM1 in a CXCL12-dependent manner. Our data reveal previously unknown roles in CXCR4-dependent chemotaxis for β-arrestin1 and STAM1, which we propose act in concert to regulate FAK signaling. The β-arrestin1·STAM1 complex is a promising target for blocking CXCR4-promoted FAK autophosphorylation and chemotaxis.

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