Skip to main content
Journal cover image

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

Publication ,  Journal Article
Firulli, BA; Howard, MJ; McDaid, JR; McIlreavey, L; Dionne, KM; Centonze, VE; Cserjesi, P; Virshup, DM; Firulli, AB
Published in: Mol Cell
November 2003

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 B56delta specifically interacts with HAND1 and -2, but not other bHLH proteins. PKA and PKC phosphorylate HAND proteins in vivo, and only B56delta-containing PP2A complexes reduce levels of HAND1 phosphorylation. During RCHOI trophoblast stem cell differentiation, B56delta 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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Mol Cell

DOI

ISSN

1097-2765

Publication Date

November 2003

Volume

12

Issue

5

Start / End Page

1225 / 1237

Location

United States

Related Subject Headings

  • Zebrafish Proteins
  • Two-Hybrid System Techniques
  • Transcription, Genetic
  • Transcription Factors
  • Stem Cells
  • Sequence Alignment
  • Recombinant Fusion Proteins
  • Protein Subunits
  • Protein Phosphatase 2
  • Protein Kinase C
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Firulli, B. A., Howard, M. J., McDaid, J. R., McIlreavey, L., Dionne, K. M., Centonze, V. E., … Firulli, A. B. (2003). PKA, PKC, and the protein phosphatase 2A influence HAND factor function: a mechanism for tissue-specific transcriptional regulation. Mol Cell, 12(5), 1225–1237. https://doi.org/10.1016/s1097-2765(03)00425-8
Firulli, Beth A., Marthe J. Howard, Jennifer R. McDaid, Leanne McIlreavey, Karen M. Dionne, Victoria E. Centonze, Peter Cserjesi, David M. Virshup, and Anthony B. Firulli. “PKA, PKC, and the protein phosphatase 2A influence HAND factor function: a mechanism for tissue-specific transcriptional regulation.Mol Cell 12, no. 5 (November 2003): 1225–37. https://doi.org/10.1016/s1097-2765(03)00425-8.
Firulli BA, Howard MJ, McDaid JR, McIlreavey L, Dionne KM, Centonze VE, et al. PKA, PKC, and the protein phosphatase 2A influence HAND factor function: a mechanism for tissue-specific transcriptional regulation. Mol Cell. 2003 Nov;12(5):1225–37.
Firulli, Beth A., et al. “PKA, PKC, and the protein phosphatase 2A influence HAND factor function: a mechanism for tissue-specific transcriptional regulation.Mol Cell, vol. 12, no. 5, Nov. 2003, pp. 1225–37. Pubmed, doi:10.1016/s1097-2765(03)00425-8.
Firulli BA, Howard MJ, McDaid JR, McIlreavey L, Dionne KM, Centonze VE, Cserjesi P, Virshup DM, Firulli AB. PKA, PKC, and the protein phosphatase 2A influence HAND factor function: a mechanism for tissue-specific transcriptional regulation. Mol Cell. 2003 Nov;12(5):1225–1237.
Journal cover image

Published In

Mol Cell

DOI

ISSN

1097-2765

Publication Date

November 2003

Volume

12

Issue

5

Start / End Page

1225 / 1237

Location

United States

Related Subject Headings

  • Zebrafish Proteins
  • Two-Hybrid System Techniques
  • Transcription, Genetic
  • Transcription Factors
  • Stem Cells
  • Sequence Alignment
  • Recombinant Fusion Proteins
  • Protein Subunits
  • Protein Phosphatase 2
  • Protein Kinase C