Regulation of casein kinase 2 by direct interaction with cell surface receptor CD5.
The transmembrane protein CD5, expressed on all T cells and the B1 subset of B cells, modulates antigen receptor-mediated activation. We used the yeast two-hybrid system to identify proteins that interact with its cytoplasmic domain and play a role in CD5 proximal signaling events. We found that the beta subunit of the serine/threonine kinase casein kinase 2 (CK2) interacts specifically with the cytoplasmic domain of CD5. Co-immunoprecipitation experiments showed activation-independent association of CK2 with CD5 in human and murine B and T cell lines and murine splenocytes. The interaction of CK2 holoenzyme with CD5 is mediated by the amino terminus of the regulatory subunit beta. CK2 binds and phosphorylates CD5 at the CK2 motifs flanked by Ser459 and Ser461. Cross-linking of CD5 leads to the activation of CD5-associated CK2 in a murine B-lymphoma cell line and a human T-leukemia cell line and is independent of net recruitment of CK2 to CD5. In contrast, CK2 is not activated following cross-linking of the B cell receptor complex or the T cell receptor complex. This direct regulation of CK2 by a cell surface receptor provides a novel pathway for control of cell activation that could play a significant role in regulation of CD5-dependent antigen receptor activation in T and B cells.
Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. craman@uab.edu
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C
Raman
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A
Kuo
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J
Deshane
D W
DW
Litchfield
R P
RP
Kimberly
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018956:CD5 Antigens / Q000378:metabolism*; D047390:Casein Kinase II; D003432:Cross-Linking Reagents / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D018956:CD5 Antigens; D003432:Cross-Linking Reagents; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases