Thymocyte activation induces the association of the proto-oncoprotein c-cbl and ras GTPase-activating protein with CD5.
Studies of knockout mice indicate that the glycoprotein CD5, which is expressed on Tcells, most thymocytes and a subset of B cells, down-regulates TCR- and B cell receptor (BCR)-mediated signaling. CD5 is associated with the TCR and BCR, and is phosphorylated on cytoplasmic tyrosine residues following antigen receptor ligation. Cross-linking of CD5 or pervanadate stimulation of thymocytes induces the association of a 120-kDa tyrosine-phosphorylated protein with CD5. The proto-oncoprotein c-cbl associates with CD5 in pervanadate-stimulated thymocytes, and reprecipitation analysis demonstrates that the major proportion of CD5-associated pp120 is c-cbl. The GTPase-activating protein for ras (ras GAP), which is not tyrosine phosphorylated following CD5 cross-linking, associates with CD5 in pervanadate-stimulated thymocytes. Using tyrosine-phosphorylated peptides we show that ras GAP interacts in an SH2-mediated manner with the phosphorylated Y429SQP sequence of CD5. Both c-cbl and ras GAP have been proposed to suppress receptor-mediated signaling, and may contribute to CD5-mediated suppression of TCR or BCR signaling.
Dennehy
K M
KM
MRC Centre for Molecular and Cellular Biology, University of Stellenbosch Medical School, Tygerberg, South Africa.
Broszeit
R
R
Ferris
W F
WF
Beyers
A D
AD
D000595:Amino Acid Sequence; D000818:Animals; D018956:CD5 Antigens / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020558:GTP Phosphohydrolases / Q000378:metabolism; D020690:GTPase-Activating Proteins; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010748:Phosphopeptides / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050721:Proto-Oncogene Proteins c-cbl; D051381:Rats; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases; D020703:ras GTPase-Activating Proteins; D018631:ras Proteins / Q000378:metabolism; D018909:src Homology Domains / Q000276:immunology
D018956:CD5 Antigens; D015815:Cell Adhesion Molecules; D020690:GTPase-Activating Proteins; D010748:Phosphopeptides; D011506:Proteins; D011518:Proto-Oncogene Proteins; D020703:ras GTPase-Activating Proteins; D014443:Tyrosine; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C496051:Ptk2 protein, mouse; C496052:Ptk2 protein, rat; D020558:GTP Phosphohydrolases; D018631:ras Proteins; C067419:CBL protein, human; C493849:Cbl protein, mouse