Involvement of Wiskott-Aldrich Syndrome Protein (WASP) in B cell antigen receptor and Btk signaling pathway

Bruton's tyrosine kinase (Btk) is a cytoplasmic tyrosine kinase which is involved in the pathogenesis of human and murine B cell deficiencies. In this study, we attempted to identify the downstream molecule in the Btk signaling pathway. We showed that WASP physically associated with Btk in B-lineage cells and was constitutively phosphorylated on its tyrosine in a preB cell line in which the tyrosine-phosphorylation of Btk was also prominent WASP was shown to be phosphorylated by Btk in cotransfection system. The phosphotyrosine motif of WASP was distinctly similar to that of the autophosphorylation site of Btk. Furthermore, WASP was shown to be tyrosine-phosphorylated upon B cell antigen receptor crosslinking. These results indicate a physical and functional link of Btk and WASP, and also suggest a possible involvement of WASP in the antigen receptor signaling pathway in B-lineage cells together with Btk.