The adaptor protein SH2D1A regulates signaling through CD150 (SLAM) in B cells.
The CD150 receptor is expressed on activated T and B lymphocytes, dendritic cells, and monocytes. A TxYxxV/I motif in the CD150 cytoplasmic tail can bind different SH2-containing molecules, including tyrosine and inositol phosphatases, Src family kinases, and adaptor molecules. To analyze CD150-initiated signal transduction pathways, we used DT40 B-cell sublines deficient in these molecules. CD150 ligation on DT40 transfectants induced the extracellular signal-regulated kinase (ERK) pathway, which required SH2-containing inositol phosphatase (SHIP) but not SH2 domain protein 1A (SH2D1A). CD150-mediated Akt phosphorylation required Syk and SH2D1A, was negatively regulated by Lyn and Btk, but was SHIP independent. Lyn directly phosphorylated Y327 in CD150, but the Akt pathway did not depend on CD150 tyrosine phosphorylation and CD150-SHP-2 association. Analysis of CD150 and SH2D1A expression in non-Hodgkin and Hodgkin lymphomas revealed stages of B-cell differentiation where these molecules are expressed alone or coexpressed. Signaling studies in Hodgkin disease cell lines showed that CD150 is linked to the ERK and Akt pathways in neoplastic B cells. Our data support the hypothesis that CD150 and SH2D1A are coexpressed during a narrow window of B-cell maturation and SH2D1A may be involved in regulation of B-cell differentiation via switching of CD150-mediated signaling pathways.
Signal Transduction Laboratory, R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology National Academy of Sciences of Ukraine, 45 Vasylkivska St, Kiev 03022, Ukraine.
Svitlana V
SV
Mikhalap
Larysa M
LM
Shlapatska
Olga V
OV
Yurchenko
Maria Y
MY
Yurchenko
Ganna G
GG
Berdova
Kim E
KE
Nichols
Edward A
EA
Clark
Svetlana P
SP
Sidorenko
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D017931:DNA Primers; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000276:immunology / Q000502:physiology; D011956:Receptors, Cell Surface; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D015703:Antigens, CD; D017931:DNA Primers; D006023:Glycoproteins; D007136:Immunoglobulins; D047908:Intracellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface; C114953:SH2D1A protein, human; C000604059:SLAMF1 protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1