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Regulation of casein kinase 2 by direct interaction with cell surface receptor CD5
1Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. craman@uab.edu
Abstract:
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.
Insights
The transmembrane protein CD5 interacts with casein kinase 2 (CK2), a key enzyme in cell signaling. This interaction directly regulates CK2 activity, influencing T and B cell activation via CD5.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- CD5 is a transmembrane protein crucial for T and B cell activation.
- Its cytoplasmic domain plays a role in proximal signaling events.
Purpose of the Study:
- To identify proteins interacting with the CD5 cytoplasmic domain.
- To elucidate the role of these interactions in CD5 signaling.
Main Methods:
- Yeast two-hybrid system for protein interaction screening.
- Co-immunoprecipitation assays to confirm protein association.
- In vitro kinase assays to assess enzyme activity.
Main Results:
- The beta subunit of casein kinase 2 (CK2) specifically binds to the CD5 cytoplasmic domain.
- CK2 associates with CD5 independently of cell activation.
- CD5 phosphorylation by CK2 occurs at specific serine residues.
- CD5 cross-linking activates associated CK2, independent of CK2 recruitment.
Conclusions:
- CD5 directly interacts with and regulates the activity of CK2.
- This novel pathway provides a mechanism for CD5-mediated control of T and B cell activation.
- The findings offer insights into immune receptor signaling and regulation.