Publication Date:
1998-06-20
Description:
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).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Westphal, R S -- Anderson, K A -- Means, A R -- Wadzinski, B E -- GM33976/GM/NIGMS NIH HHS/ -- GM51366/GM/NIGMS NIH HHS/ -- HD07503/HD/NICHD NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1998 May 22;280(5367):1258-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9596578" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antigens, Polyomavirus Transforming/metabolism
;
Brain/enzymology
;
Calcium/metabolism
;
Calcium-Calmodulin-Dependent Protein Kinase Type 4
;
Calcium-Calmodulin-Dependent Protein Kinases/genetics/isolation &
;
purification/*metabolism
;
Calmodulin/metabolism
;
Coenzymes/metabolism
;
Cyclic AMP Response Element-Binding Protein/metabolism
;
Enzyme Activation
;
Humans
;
Jurkat Cells
;
Lymphocyte Activation
;
Mutation
;
Phosphoprotein Phosphatases/isolation & purification/*metabolism
;
Phosphorylation
;
Protein Phosphatase 2
;
Rats
;
Recombinant Fusion Proteins/metabolism
;
*Signal Transduction
;
T-Lymphocytes/*enzymology
;
Transcription, Genetic
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
