A novel lipid-anchored A-kinase anchoring protein facilitates cAMP-responsive membrane events

Lain D.C. Fraser, Steven J. Tavalin, Linda B. Lester, Lorene K. Langeberg, Ann M. Westphal, Rebecca A. Dean, Neil V. Marrion, John D. Scott

Research output: Contribution to journalArticlepeer-review

246 Scopus citations

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 β cell line (RINm5F), suggesting that membrane anchoring of the kinase participates in physiologically relevant cAMP-responsive events that may involve ion channel activation.

Original languageEnglish (US)
Pages (from-to)2261-2272
Number of pages12
JournalEMBO Journal
Volume17
Issue number8
DOIs
StatePublished - Apr 15 1998

Keywords

  • AKAP18
  • Insulin secretion
  • Kinase anchoring
  • L-type Ca channel
  • Lipid modification

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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