Functional complementation of BLNK by SLP-76 and LAT linker proteins

Recent studies have demonstrated a requirement for the SLP-76 (SH2 domain-c ontaining leukocyte protein of 76 kDa) and LAT (linker for activation of ce lls) adaptor/linker proteins in T cell antigen receptor activation and T ce ll development as well as the BLNK. (B cell linker) linker protein in B cel l antigen receptor (BCR) signal transduction and B cell development. Wherea s the SLP-76 and LAT adaptor proteins are expressed in T, natural killer, a nd myeloid cells and platelets, BLNK is preferentially expressed in B cells and monocytes, Although BLNK is structurally homologous to SLP-76, BLNK in teracts with a variety of downstream signaling proteins that interact direc tly with both SLP-76 and LAT, Here, we demonstrate that neither SLP-76 nor LAT alone is sufficient to restore the signaling deficits observed in BLNK- deficient B cells. Conversely, the coexpression of SLP-76 and LAT together restored BCR-inducible calcium responses as well as activation of all three families of mitogen-activated protein kinases, Together, these data sugges t functional complementation of SLP-76 and LAT in T cell antigen receptor f unction with BLNK in BCR function.