Identification of functionally relevant phoshorylatable serine clusters in the cytoplasmic region of the human CD6 lymphocyte surface receptor.

CD6 is a transmembrane receptor expressed by all T and a subset of B lymphocytes, where it physically associates with the antigen-specific receptor to modulate activation and differentiation processes through still poorly understood mechanisms. Its cytoplasmic tail lacks intrinsic catalytic activity but presents several consensus motifs for phosphorylation. The present work reports on the identification of two constitutively phosphorylated serine clusters (S480/482/484 and S560/562/565/567/568), which are embedded into Casein Kinase 2 consensus motifs, and are indispensable for proper mitogen-activated protein kinase activation following CD6 ligation. The data point to a novel level of regulation of CD6 function by intracytoplasmic serine phosphorylation.