Gravin dynamics regulates the subcellular distribution of PKA

Xiaohong Yan, Magdalena Walkiewicz, Jennifer Carlson, Laura Leiphon, Bryon Grove

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Gravin, a multivalent A-kinase anchoring protein (AKAP), localizes to the cell periphery in several cell types and is postulated to target PKA and other binding partners to the plasma membrane. An N-terminal myristoylation sequence and three regions rich in basic amino acids are proposed to mediate this localization. Reports indicating that phorbol ester affects the distribution of SSeCKS, the rat orthologue of gravin, further suggest that PKC may also regulate the subcellular distribution of gravin, which in turn may affect PKA distribution. In this study, quantitative confocal microscopy of cells expressing full-length and mutant gravin-EGFP constructs lacking the proposed targeting domains revealed that either the N-myristoylation site or the polybasic regions were sufficient to target gravin to the cell periphery. Moreover, phorbol ester treatment induced redistribution of gravin-EGFP from the cell periphery to a juxtanuclear vesicular compartment, but this required the presence of the N-myristoylation site. Confocal microscopy further revealed that not only did gravin-EGFP target a PKA RII-ECFP construct to the cell periphery, but PKC activation resulted in redistribution of the gravin and PKA constructs to the same subcellular site. It is postulated that this dynamic response by gravin to PKC activity may mediate PKC dependent control of PKA activity.

Original languageEnglish (US)
Pages (from-to)1247-1259
Number of pages13
JournalExperimental Cell Research
Volume315
Issue number7
DOIs
StatePublished - Apr 15 2009

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Keywords

  • AKAP12
  • Confocal microscopy
  • Fluorescent proteins
  • Gravin
  • PKA
  • PKC

ASJC Scopus subject areas

  • Cell Biology

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