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A signaling complex of Ca2+-calmodulin-dependent protein kinase IV and protein phosphatase 2A.

Publication ,  Journal Article
Westphal, RS; Anderson, KA; Means, AR; Wadzinski, BE
Published in: Science
May 22, 1998

Stimulation of T lymphocytes results in a rapid increase in intracellular calcium concentration ([Ca2+]i) that parallels the activation of Ca2+-calmodulin-dependent protein kinase IV (CaMKIV), a nuclear enzyme that can phosphorylate and activate the cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB). However, inactivation of CaMKIV occurs despite the sustained increase in [Ca2+]i that is required for T cell activation. A stable and stoichiometric complex of CaMKIV with protein serine-threonine phosphatase 2A (PP2A) was identified in which PP2A dephosphorylates CaMKIV and functions as a negative regulator of CaMKIV signaling. In Jurkat T cells, inhibition of PP2A activity by small t antigen enhanced activation of CREB-mediated transcription by CaMKIV. These findings reveal an intracellular signaling mechanism whereby a protein serine-threonine kinase (CaMKIV) is regulated by a tightly associated protein serine-threonine phosphatase (PP2A).

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Published In

Science

DOI

ISSN

0036-8075

Publication Date

May 22, 1998

Volume

280

Issue

5367

Start / End Page

1258 / 1261

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • T-Lymphocytes
  • Signal Transduction
  • Recombinant Fusion Proteins
  • Rats
  • Protein Phosphatase 2
  • Phosphorylation
  • Phosphoprotein Phosphatases
  • Mutation
  • Lymphocyte Activation
 

Citation

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Westphal, R. S., Anderson, K. A., Means, A. R., & Wadzinski, B. E. (1998). A signaling complex of Ca2+-calmodulin-dependent protein kinase IV and protein phosphatase 2A. Science, 280(5367), 1258–1261. https://doi.org/10.1126/science.280.5367.1258
Westphal, R. S., K. A. Anderson, A. R. Means, and B. E. Wadzinski. “A signaling complex of Ca2+-calmodulin-dependent protein kinase IV and protein phosphatase 2A.Science 280, no. 5367 (May 22, 1998): 1258–61. https://doi.org/10.1126/science.280.5367.1258.
Westphal RS, Anderson KA, Means AR, Wadzinski BE. A signaling complex of Ca2+-calmodulin-dependent protein kinase IV and protein phosphatase 2A. Science. 1998 May 22;280(5367):1258–61.
Westphal, R. S., et al. “A signaling complex of Ca2+-calmodulin-dependent protein kinase IV and protein phosphatase 2A.Science, vol. 280, no. 5367, May 1998, pp. 1258–61. Pubmed, doi:10.1126/science.280.5367.1258.
Westphal RS, Anderson KA, Means AR, Wadzinski BE. A signaling complex of Ca2+-calmodulin-dependent protein kinase IV and protein phosphatase 2A. Science. 1998 May 22;280(5367):1258–1261.
Journal cover image

Published In

Science

DOI

ISSN

0036-8075

Publication Date

May 22, 1998

Volume

280

Issue

5367

Start / End Page

1258 / 1261

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • T-Lymphocytes
  • Signal Transduction
  • Recombinant Fusion Proteins
  • Rats
  • Protein Phosphatase 2
  • Phosphorylation
  • Phosphoprotein Phosphatases
  • Mutation
  • Lymphocyte Activation