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

Journal Article

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).

Full Text

Duke Authors

Cited Authors

  • Westphal, RS; Anderson, KA; Means, AR; Wadzinski, BE

Published Date

  • May 22, 1998

Published In

Volume / Issue

  • 280 / 5367

Start / End Page

  • 1258 - 1261

PubMed ID

  • 9596578

International Standard Serial Number (ISSN)

  • 0036-8075

Language

  • eng

Conference Location

  • United States