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 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).
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Related Subject Headings
- Transcription, Genetic
- T-Lymphocytes
- Signal Transduction
- Recombinant Fusion Proteins
- Rats
- Protein Phosphatase 2
- Phosphorylation
- Phosphoprotein Phosphatases
- Mutation
- Lymphocyte Activation
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Transcription, Genetic
- T-Lymphocytes
- Signal Transduction
- Recombinant Fusion Proteins
- Rats
- Protein Phosphatase 2
- Phosphorylation
- Phosphoprotein Phosphatases
- Mutation
- Lymphocyte Activation