Functional association of CD7 with phosphatidylinositol 3-kinase: interaction via a YEDM motif

Abstract

Human CD7 is a 40 kDa protein expressed on thymocytes, early T, B, 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 cell activation and/or adhesion, and that CD7-mediated cell activation may be transduced via the lipid kinase phosphatldyllnositol 3-kinase (PI3-klnase), a heterodimerlc cytosollc protein consisting of an 85 kDa adaptor subunit that is coupled to a 110 kDa catalytic subunit. It has recently been shown that a sequence motif present in the cytoplasmic tail of both human and mouse CD7 bound with high affinity to recombinant SH2 domains present in the p85 subunit of PI3-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 that the cytoplasmic tall of CD7 interacts with a functional PI3-kJnase via the pTyr-X-X-Met motif. Furthermore, we show that cross-linking of CD7 markedly increased the amount of PI3-kinase activity associated with CD7. The Interaction of CD7 with the PI3-kinase signal transduction pathway provides a mechanism for the previously observed functional responses attributed to CD7-mediated T and NK cell activation.