| First Author | Fraser ID | Year | 1998 |
| Journal | EMBO J | Volume | 17 |
| Issue | 8 | Pages | 2261-72 |
| PubMed ID | 9545239 | Mgi Jnum | J:47378 |
| Mgi Id | MGI:1203361 | Doi | 10.1093/emboj/17.8.2261 |
| Citation | Fraser ID, et al. (1998) A novel lipid-anchored A-kinase Anchoring Protein facilitates cAMP-responsive membrane events. EMBO J 17(8):2261-72 |
| abstractText | 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 anchor-ing 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. |
