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PMID: 9545239 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The EMBO journal ·Vol. 17 ·No. 8 ·1998-04-15 ·Pages 2261-72

Fraser ID, Tavalin SJ, Lester LB, Langeberg LK, Westphal AM, Dean RA, Marrion NV, Scott JD

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.

MeSH Terms
A Kinase Anchor Proteins Adaptor Proteins, Signal Transducing Amino Acid Sequence Animals Base Sequence Binding Sites Calcium Channels/physiology Carrier Proteins Cell Line Cell Membrane/metabolism Cloning, Molecular Cyclic AMP/metabolism Cyclic AMP-Dependent Protein Kinases/metabolism DNA, Complementary Electric Conductivity Glucagon/metabolism Glucagon-Like Peptide 1 Humans Insulin/metabolism Insulin Secretion Membrane Proteins Mice Molecular Sequence Data Peptide Fragments/metabolism Peptide Mapping Protein Kinases/genetics,metabolism Protein Precursors/metabolism Sequence Homology, Amino Acid
Chemicals
A Kinase Anchor Proteins AKAP7 protein, human Adaptor Proteins, Signal Transducing Akap7 protein, mouse Calcium Channels Carrier Proteins DNA, Complementary Insulin Membrane Proteins Peptide Fragments Protein Precursors Glucagon-Like Peptide 1 Glucagon Cyclic AMP Protein Kinases Cyclic AMP-Dependent Protein Kinases
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Fraser I D
Howard Hughes Medical Institute, Oregon Health Sciences University, Portland, OR 97201, USA.
Tavalin S J
Lester L B
Langeberg L K
Westphal A M
Dean R A
Marrion N V
Scott J D
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/17.8.2261
Published
1998-04-15
Pages
2261-72
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1170570
Subset
IM
Grants
NINDS NIH HHS · F32 NS010202 · United States
NIDDK NIH HHS · DK02353 · United States
NINDS NIH HHS · NS07381 · United States
NINDS NIH HHS · NS10202 · United States
Databases
GENBANK
AF047715, AF047716
External Links
PubMed source DOI: 10.1093/emboj/17.8.2261 PMC Full Text View journal details
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