Nuclear localization of type II cAMP-dependent protein kinase during limb cartilage differentiation is associated with a novel developmentally regulated A-kinase anchoring protein

Qihang Zhang, Daniel W. Carr, Kenneth M. Lerea, John D. Scott, Stuart A. Newman

Research output: Contribution to journalArticle

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Abstract

Differentiation of chicken limb cartilage is accompanied by a rise in intracellular cyclic AMP, an inducer of cartilage-specific gene expression. A basic ~ 35-kDa protein, designated p35, is the major nuclear substrate for cAMP-dependent protein kinase (PKA) during this process. Here we show that whereas both precartilage and cartilage nuclei contain p35, only precartilage nuclei contain PKA. The phosphorylation of p35 in isolated cell fractions was used as an index of changes in the cellular comparmentalization of components of PKA during chondrogenesis. Both the catalytic subunit and type II regulatory subunit (RII) of PKA were present in the precartilage nuclear fraction, but were undetectable or present in only trace amounts in the cartilage nuclear fraction. furthermore, a novel ~ 150-kDa A-kinase anchoring protein (AKAP), which binds to RII, was detected in the nuclear matrix of precartilage nuclei but, like RII, was virtually absent in the nuclei of fully differentiated cartilage cells. In limb mesenchymal cells undergoing chondrogenesis in culture a corresponding set of changes occurred: cartilage differentiation was accompanied by a marked reduction in the amounts of both nuclear RII and nAKAP150. These observations indicate that type II PKA holoenzyme is imported into the mesenchymal cell nucleus prior to chondrogenesis, an event that appears to depend on the the activity of the developmentally regulated nAKAP150.

Original languageEnglish (US)
Pages (from-to)51-61
Number of pages11
JournalDevelopmental Biology
Volume176
Issue number1
DOIs
StatePublished - May 25 1996

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ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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