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

Westphal RS, Anderson KA, Means AR, Wadzinski BE
Science. 1998 280 (5367): 1258-61

PMID: 9596578 · 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).

MeSH Terms (22)

Animals Antigens, Polyomavirus Transforming Brain Calcium Calcium-Calmodulin-Dependent Protein Kinases Calcium-Calmodulin-Dependent Protein Kinase Type 4 Calmodulin Coenzymes Cyclic AMP Response Element-Binding Protein Enzyme Activation Humans Jurkat Cells Lymphocyte Activation Mutation Phosphoprotein Phosphatases Phosphorylation Protein Phosphatase 2 Rats Recombinant Fusion Proteins Signal Transduction T-Lymphocytes Transcription, Genetic

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