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. 1998 Apr 15;17(8):2261–2272. doi: 10.1093/emboj/17.8.2261

A novel lipid-anchored A-kinase Anchoring Protein facilitates cAMP-responsive membrane events.

I D Fraser 1, S J Tavalin 1, L B Lester 1, L K Langeberg 1, A M Westphal 1, R A Dean 1, N V Marrion 1, J D Scott 1
PMCID: PMC1170570  PMID: 9545239

Abstract

Compartmentalization of protein kinases with substrates is a mechanism that may promote specificity of intracellular phosphorylation events. We have cloned a low-molecular weight A-kinase Anchoring Protein, called AKAP18, which targets the cAMP-dependent protein kinase (PKA) to the plasma membrane, and permits functional coupling to the L-type calcium channel. Membrane anchoring is mediated by the first 10 amino acids of AKAP18, and involves residues Gly1, Cys4 and Cys5 which are lipid-modified through myristoylation and dual palmitoylation, respectively. Transient transfection of AKAP18 into HEK-293 cells expressing the cardiac L-type Ca2+ channel promoted a 34 9% increase in cAMP-responsive Ca2+ currents. In contrast, a targeting-deficient mutant of AKAP18 had no effect on Ca2+ currents in response to the application of a cAMP analog. Further studies demonstrate that AKAP18 facilitates GLP-1-mediated insulin secretion in a pancreatic beta cell line (RINm5F), suggesting that membrane anchoring of the kinase participates in physiologically relevant cAMP-responsive events that may involve ion channel activation.

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Selected References

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