title: BANK1 and BLK act through phospholipase C gamma 2 in B-cell signaling.
abstract: The B cell adaptor protein with ankyrin repeats (BANK1) and the B lymphoid tyrosine kinase (BLK) have been genetically associated with autoimmunity. The proteins of these genes interact physically and work in concert during B-cell signaling. Little is know about their interactions with other B-cell signaling molecules or their role in the process. Using yeast two hybrid (Y2H) we sought for factors that interact with BANK1. We found that the molecular switch PLCg2 interacts with BANK1 and that the interaction is promoted by B-cell receptor (BCR) stimulation. We found further that the kinase activity of BLK enhanced BANK1- PLCg2 binding and that the interaction was suppressed upon BLK depletion. Immunoprecipitation and mutational analysis demonstrated that the interaction between BANK1 and PLCg2 was dependent on specific tyrosine and proline residues on the adaptor protein. Our results provide new information important to understand the role of these two genes in basic B-cell physiology and immune-related diseases.
authors.affiliation: Centro de Genómica e Investigación Oncológica, Pfizer-Universidad de Granada-Junta de Andalucía, Granada, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Bernal-Quirós
authors.forename: Ying-Yu
authors.initials: YY
authors.lastname: Wu
authors.forename: Marta E
authors.initials: ME
authors.lastname: Alarcón-Riquelme
authors.forename: Casimiro
authors.initials: C
authors.lastname: Castillejo-López
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology*; D003001:Cloning, Molecular; D016000:Cluster Analysis; D015971:Gene Expression Regulation, Enzymologic; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007075:Immunoglobulin M / Q000737:chemistry; D008565:Membrane Proteins / Q000378:metabolism*; D009154:Mutation; D051966:Phospholipase C gamma / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D020798:Two-Hybrid System Techniques; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C447641:BANK1 protein, human; D007075:Immunoglobulin M; D008565:Membrane Proteins; D049452:Green Fluorescent Proteins; C082599:protein-tyrosine kinase p55(blk); D019061:src-Family Kinases; D051966:Phospholipase C gamma
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