REGULATION OF CASEIN KINASE-2 BY DIRECT INTERACTION WITH CELL-SURFACERECEPTOR CD5

The transmembrane protein CD5, expressed on all T cells and the B1 sub set of B cells, modulates antigen receptor-mediated activation. We use d the yeast two-hybrid system to identify proteins that interact with its cytoplasmic domain and play a role in CD5 proximal signaling event s. We found that the beta subunit of the serine/threonine kinase casei n kinase 2 (CK2) interacts specifically with the cytoplasmic domain of CD5. Coimmunoprecipitation 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 med iated by the amino terminus of the regulatory subunit beta. CK2 binds and phosphorylates CD5 at the CK2 motifs flanked by Ser(459) and Ser(4 61). Cross-linking of CD5 bads 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 o r the T cell receptor complex. This direct regulation of CK2 by a cell surface receptor provides a novel pathway for control of cell activat ion that could play a significant role in regulation of CD5-dependent antigen receptor activation in T and B cells.