mAKAP: An A-kinase anchoring protein targeted to the nuclear membrane of differentiated myocytes

Michael S. Kapiloff, Robynn V. Schillace, Ann M. Westphal, John D. Scott

Research output: Contribution to journalArticle

136 Scopus citations

Abstract

The compartmentalization of second messenger-activated protein kinases contributes to the fidelity of hormone-mediated signal transduction events. For example, the cAMP-dependent protein kinase is tethered at specific intracellular locations through association with A-kinase anchoring proteins (AKAPs). We now report the cloning of mAKAP, an anchoring protein found predominantly in heart, skeletal muscle and brain, and whose expression is induced in neonatal ventriculocytes by treatment with hypertrophic stimuli. mAKAP is targeted to the nuclear membrane of differentiated myocytes. Analysis of mAKAP-green fluorescent protein (GFP) fusion constructs revealed that nuclear membrane targeting is conferred by two regions of the protein, between residues 772-915 and 915-1065, which contain spectrin-like repeat sequences. Heterologous expression of the mAKAP targeting sequences displaced the endogenous anchoring protein from the nuclear membrane, demonstrating that mAKAP targeting is saturable. Collectively, these data suggest that a domain containing spectrin-like repeats mediates targeting of the anchoring protein mAKAP and the cAMP-dependent protein kinase holoenzyme to the nuclear membrane in response to differentiation signals.

Original languageEnglish (US)
Pages (from-to)2725-2736
Number of pages12
JournalJournal of Cell Science
Volume112
Issue number16
StatePublished - Sep 22 1999

Keywords

  • AKAP
  • Differentiation
  • Heart
  • Protein kinase A
  • Spectrin repeat

ASJC Scopus subject areas

  • Cell Biology

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    Kapiloff, M. S., Schillace, R. V., Westphal, A. M., & Scott, J. D. (1999). mAKAP: An A-kinase anchoring protein targeted to the nuclear membrane of differentiated myocytes. Journal of Cell Science, 112(16), 2725-2736.