Letter abstract
Nature Cell Biology 9, 415 - 421 (2007)
Published online: 18 March 2007 | doi:10.1038/ncb1561
4 Integrins are Type I cAMP-dependent protein kinase-anchoring proteins
Chinten James Lim1, Jaewon Han1, Nima Yousefi1, Yuliang Ma2, Paul S. Amieux3, G. Stanley McKnight3, Susan S. Taylor2 & Mark H. Ginsberg1
A-kinase anchoring proteins (AKAPs) control the localization and substrate specificity of cAMP-dependent protein kinase (PKA), tetramers of regulatory (PKA-R) and catalytic (PKA-C) subunits, by binding to PKA-R subunits1. Most mammalian AKAPs bind Type II PKA through PKA-RII (ref. 2), whereas dual specificity AKAPs bind both PKA-RI and PKA-RII (ref. 3). Inhibition of PKA–AKAP interactions modulates PKA signalling2. Localized PKA activation in pseudopodia of migrating cells4 phosphorylates 
4 integrins to provide spatial cues governing cell motility5. Here, we report that the 4 cytoplasmic domain is a Type I PKA-specific AKAP that is distinct from canonical AKAPs in two ways: the 4 interaction requires the PKA holoenzyme, and is insensitive to amphipathic peptides that disrupt most PKA–AKAP interactions. We exploited type-specific PKA anchoring peptides to create genetically encoded baits that sequester specific PKA isoforms to the mitochondria and found that mislocalization of Type I, but not Type II, PKA disrupts 4 phosphorylation and markedly inhibits the velocity and directional persistence of cell migration.
- Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
- Department of Chemistry and Biochemistry and Howard Hughes Medical Institute, University of California San Diego, La Jolla, CA 92093, USA.
- Department of Pharmacology, University of Washington, Seattle, WA 98195, USA.
Correspondence to: Mark H. Ginsberg1 e-mail: mhginsberg@ucsd.edu
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