PMID:8107230

Citation	Mosialos, G, Hanissian, SH, Jawahar, S, Vara, L, Kieff, E and Chatila, TA (1994) A Ca2+/calmodulin-dependent protein kinase, CaM kinase-Gr, expressed after transformation of primary human B lymphocytes by Epstein-Barr virus (EBV) is induced by the EBV oncogene LMP1. J. Virol. 68:1697-705
Abstract	CaM kinase-Gr is a multifunctional Ca2+/calmodulin-dependent protein kinase which is enriched in neurons and T lymphocytes. The kinase is absent from primary human B lymphocytes but is expressed in Epstein-Barr virus (EBV)-transformed B-lymphoblastoid cell lines, suggesting that expression of the kinase can be upregulated by an EBV gene product(s). We investigated the basis of CaM kinase-Gr expression in EBV-transformed cells and the mechanisms that regulate its activity therein by using an EBV-negative Burkitt lymphoma cell line, BJAB, and BJAB cells converted to expression of individual EBV proteins by single-gene transfer. CaM kinase-Gr expression was upregulated in BJAB cells by EBV latent-infection membrane protein 1 (LMP1) but not by LMP2A or by nuclear proteins EBNA1, EBNA2, EBNA3A, and EBNA3C. In LMP1-converted BJAB cells, the kinase was functional and was dramatically activated upon cross-linking of surface immunoglobulin M. Overlapping cDNA clones that encode human CaM kinase-Gr were sequenced, revealing 81% amino acid identity between the rat and human proteins. Transfection of BJAB cells with an expression construct for the human enzyme resulted in a functional kinase which was shown by epitope tagging to localize primarily to cytoplasmic and perinuclear structures. Induction of CaM kinase-Gr expression by LMP1 provides the first example of a Ca2+/calmodulin-dependent protein kinase upregulated by a viral protein. In view of the key role played by LMP1 in B-lymphocyte immortalization by EBV, these findings implicate CaM kinase-Gr as a potential mediator of B-lymphocyte growth transformation.
Links	PubMed PMC236629
Keywords	Amino Acid Sequence; Animals; Antigens, Viral/pharmacology; B-Lymphocytes; Base Sequence; Calcium-Calmodulin-Dependent Protein Kinase Type 4; Calcium-Calmodulin-Dependent Protein Kinases/biosynthesis; Calcium-Calmodulin-Dependent Protein Kinases/genetics; Calcium-Calmodulin-Dependent Protein Kinases/isolation & purification; Cell Compartmentation; Cell Nucleus/chemistry; Cell Transformation, Viral; Cells, Cultured; Cloning, Molecular; Cross-Linking Reagents; Cytoplasm/chemistry; Enzyme Activation; Enzyme Induction; Fluorescent Antibody Technique; Gene Expression Regulation, Enzymologic/drug effects; Herpesvirus 4, Human; Humans; Immunoglobulin M/metabolism; Molecular Sequence Data; Receptors, Antigen, B-Cell/metabolism; Recombinant Proteins/biosynthesis; Sequence Homology, Amino Acid; Viral Matrix Proteins/pharmacology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:KCC4		GO:0004683: calmodulin-dependent protein kinase activity	ECO:0000314:		F		Fig 3 or 7	complete CACAO 3506
HUMAN:KCC4	enables	GO:0004683: calmodulin-dependent protein kinase activity	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete

References

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