A Signaling Complex of Ca 2+ -Calmodulin-Dependent Protein Kinase IV and Protein Phosphatase 2A
- 22 May 1998
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 280 (5367), 1258-1261
- https://doi.org/10.1126/science.280.5367.1258
Abstract
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).Keywords
This publication has 27 references indexed in Scilit:
- Regulation of Protein Phosphatase 2A by Direct Interaction with Casein Kinase 2αScience, 1997
- Differential activation of transcription factors induced by Ca2+ response amplitude and durationNature, 1997
- Molecular Identification of I1PP2A, a Novel Potent Heat-Stable Inhibitor Protein of Protein Phosphatase 2ABiochemistry, 1996
- Activation of Ca2+/Calmodulin-dependent Protein Kinase (CaM-kinase) IV by CaM-kinase Kinase in Jurkat T LymphocytesPublished by Elsevier ,1995
- Direct Demonstration of NFATp Dephosphorylation and Nuclear Localization in Activated HT-2 Cells Using a Specific NFATp Polyclonal AntibodyJournal of Biological Chemistry, 1995
- Regulation by tumour antigens defines a role for PP2A in signal transductionSeminars in Cancer Biology, 1995
- Phosphorylation and Activation of Ca2+-Calmodulin-dependent Protein Kinase IV by Ca2+-Calmodulin-dependent Protein Kinase Ia KinaseJournal of Biological Chemistry, 1995
- On growth and formNature, 1995
- Inhibitors of protein kinases and phosphatasesTrends in Biochemical Sciences, 1994
- Nuclear protein CBP is a coactivator for the transcription factor CREBNature, 1994