FUNCTIONAL ASSOCIATION OF CD7 WITH PHOSPHATIDYLINOSITOL 3-KINASE - INTERACTION VIA A YEDM MOTIF

Human CD7 is a 40 kDa protein expressed on thymocytes, early T, a, NK and myeloid lineage cells in bone marrow, and on mature T and NK cells , Previous studies suggested human CD7 may be involved in T and NK cel l activation and/or adhesion, and that CD7-mediated cell activation ma y be transduced via the lipid kinase phosphatidylinositol 3-kinase (Pl 3-kinase), a heterodimeric cytosolic protein consisting of an 85 kDa a daptor subunit that is coupled to a 110 kDa catalytic subunit. It has recently been shown that a sequence motif present in the cytoplasmic t ail of both human and mouse CD7 bound with high affinity to recombinan t SH2 domains present in the p85 subunit of Pl3-kinase. In this work, we used co-precipitation with anti-CD7 mAb 3A1 and recombinant p85 SH2 -GST fusion proteins and peptide competition analysis to demonstrate t hat the cytoplasmic tail of CD7 interacts with a functional Pl3-kinase via the pTyr-X-X-Met motif. Furthermore, we show that cross-linking o f CD7 markedly increased the amount of Pl3-kinase activity associated with CD7. The interaction of CD7 with the Pl3-kinase signal transducti on pathway provides a mechanism for the previously observed functional responses attributed to CD7-mediated T and NK cell activation.