Regulation of actin-based cell migration by cAMP/PKA.
A wide variety of soluble signaling substances utilize the cyclic AMP-dependent protein kinase (PKA) pathway to regulate cellular behaviors including intermediary metabolism, ion channel conductivity, and transcription. A growing literature suggests that integrin-mediated cell adhesion may also utilize PKA to modulate adhesion-associated events such as actin cytoskeletal dynamics and migration. PKA is dynamically regulated by integrin-mediated cell adhesion to extracellular matrix (ECM). Furthermore, while some hallmarks of cell migration and cytoskeletal organization require PKA activity (e.g. activation of Rac and Cdc42; actin filament assembly), others are inhibited by it (e.g. activation of Rho and PAK; interaction of VASP with the c-Abl tyrosine kinase). Also, cell migration and invasion can be impeded by either inhibition or hyper-activation of PKA. Finally, a number of A-kinase anchoring proteins (AKAPs) serve to associate PKA with various components of the actin cytoskeleton, thereby enhancing and/or specifying cAMP/PKA signaling in those regions. This review discusses the growing literature that supports the hypothesis that PKA plays a central role in cytoskeletal regulation and cell migration.
Howe
Alan K
AK
Department of Pharmacology, Vermont Cancer Center, University of Vermont, HSRF# 322, Burlington 05405-0075, USA. Alan.Howe@uvm.edu
D008841:Actin Cytoskeleton / Q000502:physiology*; D000199:Actins / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology*; D006801:Humans; D015398:Signal Transduction
D000199:Actins; D017868:Cyclic AMP-Dependent Protein Kinases