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

Academic Article

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 phosphatidylinositol 3-kinase (Pi3-kinase), a heterodimeric cytosolic 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 tall 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 tail of CD7 interacts with a functional Pi3-kinase 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.
  • Published In

    Keywords

  • Amino Acid Sequence, Animals, Antibodies, Monoclonal, Antigens, CD7, Binding Sites, Cross-Linking Reagents, Humans, Jurkat Cells, Killer Cells, Natural, Lymphocyte Activation, Mice, Molecular Sequence Data, Peptide Fragments, Phosphatidylinositol 3-Kinases, Phosphotransferases (Alcohol Group Acceptor), Precipitin Tests, Protein Conformation, Recombinant Fusion Proteins, Signal Transduction, T-Lymphocytes, src Homology Domains
  • Digital Object Identifier (doi)

    Author List

  • Lee DM; Patel DD; Pendergast AM; Haynes BF
  • Start Page

  • 1195
  • End Page

  • 1203
  • Volume

  • 8
  • Issue

  • 8