PKA, PKC, and the protein phosphatase 2A influence HAND factor function: A mechanism for tissue-specific transcriptional regulation

Beth A. Firulli, Marthe J. Howard, Jennifer R. McDaid, Leanne McIlreavey, Karen M. Dionne, Victoria E. Centonze, Peter Cserjesi, David M. Virshup, Anthony B. Firulli

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

The bHLH factors HAND1 and HAND2 are required for heart, vascular, neuronal, limb, and extraembryonic development. Unlike most bHLH proteins, HAND factors exhibit promiscuous dimerization properties. We report that phosphorylation/dephosphorylation via PKA, PKC, and a specific heterotrimeric protein phosphatase 2A (PP2A) modulates HAND function. The PP2A targeting-subunit B56δ specifically interacts with HAND1 and -2, but not other bHLH proteins. PKA and PKC phosphorylate HAND proteins in vivo, and only B56δ-containing PP2A complexes reduce levels of HAND1 phosphorylation. During RCHOI trophoblast stem cell differentiation, B56δ expression is downregulated and HAND1 phosphorylation increases. Mutations in phosphorylated residues result in altered HAND1 dimerization and biological function. Taken together, these results suggest that site-specific phosphorylation regulates HAND factor functional specificity.

Original languageEnglish (US)
Pages (from-to)1225-1237
Number of pages13
JournalMolecular Cell
Volume12
Issue number5
DOIs
StatePublished - Nov 2003

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'PKA, PKC, and the protein phosphatase 2A influence HAND factor function: A mechanism for tissue-specific transcriptional regulation'. Together they form a unique fingerprint.

  • Cite this

    Firulli, B. A., Howard, M. J., McDaid, J. R., McIlreavey, L., Dionne, K. M., Centonze, V. E., Cserjesi, P., Virshup, D. M., & Firulli, A. B. (2003). PKA, PKC, and the protein phosphatase 2A influence HAND factor function: A mechanism for tissue-specific transcriptional regulation. Molecular Cell, 12(5), 1225-1237. https://doi.org/10.1016/S1097-2765(03)00425-8