A signaling complex of ca2+-calmodulin-dependent protein kinase IV and protein phosphatase 2A

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 ele...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1998-05, Vol.280 (5367), p.1258-1261
Main Authors: WESTPHAL, R. S, ANDERSON, K. A, MEANS, A. R, WADZINSKI, B. E
Format: Article
Language:English
Subjects:
Animals
Antigens, Polyomavirus Transforming - metabolism
Biological and medical sciences
Brain - enzymology
Calcium - metabolism
Calcium-Calmodulin-Dependent Protein Kinase Type 4
Calcium-Calmodulin-Dependent Protein Kinases - genetics
Calcium-Calmodulin-Dependent Protein Kinases - isolation & purification
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
Calmodulin
Calmodulin - metabolism
Cell physiology
Cell research
Coenzymes - metabolism
Cyclic AMP Response Element-Binding Protein - metabolism
Cytological research
Enzyme Activation
Fundamental and applied biological sciences. Psychology
Humans
Jurkat Cells
Lymphocyte Activation
Molecular and cellular biology
Mutation
Phosphoprotein Phosphatases - isolation & purification
Phosphoprotein Phosphatases - metabolism
Phosphorylation
Protein Phosphatase 2
Rats
Recombinant Fusion Proteins - metabolism
Signal Transduction
T-Lymphocytes - enzymology
Transcription, Genetic
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Summary: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).
ISSN:0036-8075
1095-9203
DOI:10.1126/science.280.5367.1258