A Signaling Complex of Ca2+-Calmodulin-Dependent Protein Kinase IV and Protein Phosphatase 2A

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Science  22 May 1998:
Vol. 280, Issue 5367, pp. 1258-1261
DOI: 10.1126/science.280.5367.1258


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).

  • * These authors contributed equally to this report.

  • Present address: Howard Hughes Medical Institute, Vollum Institute, Oregon Health Sciences University L-474, 3181 SW Sam Jackson Park Road, Portland, OR 97201, USA.

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