CDw150 associates with src-homology 2-containing inositol phosphatase and modulates CD95-mediated apoptosis.
CDw150, a receptor up-regulated on activated T or B lymphocytes, has a key role in regulating B cell proliferation. Patients with X-linked lymphoproliferative disease have mutations in a gene encoding a protein, DSHP/SAP, which interacts with CDw150 and is expressed in B cells. Here we show that CDw150 on B cells associates with two tyrosine-phosphorylated proteins, 59 kDa and 145 kDa in size. The 59-kDa protein was identified as the Src-family kinase Fgr. The 145-kDa protein is the inositol polyphosphate 5'-phosphatase, SH2-containing inositol phosphatase (SHIP). Both Fgr and SHIP interact with phosphorylated tyrosines in CDw150's cytoplasmic tail. Ligation of CDw150 induces the rapid dephosphorylation of both SHIP and CDw150 as well as the association of Lyn and Fgr with SHIP. CD95/Fas-mediated apoptosis is enhanced by signaling via CDw150, and CDw150 ligation can override CD40-induced rescue of CD95-mediated cell death. The ability of CDw150 to regulate cell death does not correlate with serine phosphorylation of the Akt kinase, but does correlate with SHIP tyrosine dephosphorylation. Thus, the CDw150 receptor may function to regulate the fate of activated B cells via SHIP as well as via the DSHP/SAP protein defective in X-linked lymphoproliferative disease patients.
Mikhalap
S V
SV
Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, Academy of Science of Ukraine, Kiev, Ukraine.
Shlapatska
L M
LM
Berdova
A G
AG
Law
C L
CL
Clark
E A
EA
Sidorenko
S P
SP
D015703:Antigens, CD; D017209:Apoptosis; D001402:B-Lymphocytes / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D007136:Immunoglobulins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008232:Lymphoproliferative Disorders / Q000276:immunology; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011940:Receptor Aggregation; D011956:Receptors, Cell Surface; D015398:Signal Transduction; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D019014:fas Receptor / Q000378:metabolism*; D018909:src Homology Domains; D019061:src-Family Kinases
D015703:Antigens, CD; D002352:Carrier Proteins; D006023:Glycoproteins; D007136:Immunoglobulins; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D019014:fas Receptor; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D011505:Protein-Tyrosine Kinases; C053102:proto-oncogene proteins c-fgr; D019061:src-Family Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D010744:Phosphoric Monoester Hydrolases; D017493:Leukocyte Common Antigens; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases