Biomaterial Database

B cell antigen receptor (BCR)-mediated formation of a SHP-2-pp120 complex and its inhibition by Fc gamma RIIB1-BCR coligation. 1998

K Nakamura, and J C Cambier

Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.

Accumulating evidence indicates that the Src homology 2-containing tyrosine phosphatase 2 (SHP-2) plays an important role in signal transduction through receptor tyrosine kinase and cytokine receptors. In most models, SHP-2 appears to be a positive mediator of signaling. However, coligation of Fc gamma RIIB1 with B cell Ag receptors (BCR) inhibits BCR-mediated signaling by a mechanism that may involve recruitment of phosphatases SHP-1, SHP-2, and the SH2 containing inositol 5'phosphatase (SHIP) to the phosphorylated Fc gamma RIIB1 immunoreceptor tyrosine-based inhibitory motif. The role of SHP-2 in BCR-mediated cell activation and in Fc gamma RIIB1-mediated inhibitory signaling is unclear. In this study we assessed the association of SHP-2 with phosphotyrosine-containing cellular protein(s) before and after stimulation through these receptors. BCR stimulation induced the association of SHP-2 with a single major tyrosyl-phosphorylated molecule (pp120) that had an apparent molecular mass of 120 kDa. Coligation of Fc gamma RIIB1 with BCR led to a rapid decrease in SHP-2 association with pp120. Analysis of the subcellular localization of pp120 showed that the complex of SHP-2 and tyrosyl-phosphorylated p120 occurs predominantly in the cytosol. Furthermore, the binding of the two molecules was mediated by the interaction of tyrosyl-phosphorylated p120 with the SHP-2 N-terminal SH2 domain. These findings indicate that SHP-2 and pp120 function in BCR signaling, and this function may be inhibited by Fc gamma RIIB1 signaling.

UI	MeSH Term	Description	Entries
D008213	Lymphocyte Activation	Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.	Blast Transformation,Blastogenesis,Lymphoblast Transformation,Lymphocyte Stimulation,Lymphocyte Transformation,Transformation, Blast,Transformation, Lymphoblast,Transformation, Lymphocyte,Activation, Lymphocyte,Stimulation, Lymphocyte
D010766	Phosphorylation	The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.	Phosphorylations
D011505	Protein-Tyrosine Kinases	Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.	Tyrosine Protein Kinase,Tyrosine-Specific Protein Kinase,Protein-Tyrosine Kinase,Tyrosine Kinase,Tyrosine Protein Kinases,Tyrosine-Specific Protein Kinases,Tyrosylprotein Kinase,Kinase, Protein-Tyrosine,Kinase, Tyrosine,Kinase, Tyrosine Protein,Kinase, Tyrosine-Specific Protein,Kinase, Tyrosylprotein,Kinases, Protein-Tyrosine,Kinases, Tyrosine Protein,Kinases, Tyrosine-Specific Protein,Protein Kinase, Tyrosine-Specific,Protein Kinases, Tyrosine,Protein Kinases, Tyrosine-Specific,Protein Tyrosine Kinase,Protein Tyrosine Kinases,Tyrosine Specific Protein Kinase,Tyrosine Specific Protein Kinases
D011947	Receptors, Antigen, B-Cell	IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment.	Antigen Receptors, B-Cell,B-Cell Antigen Receptor,B-Cell Antigen Receptors,Surface Immunoglobulin,Immunoglobulins, Membrane-Bound,Immunoglobulins, Surface,Membrane Bound Immunoglobulin,Membrane-Bound Immunoglobulins,Receptors, Antigen, B Cell,Surface Immunoglobulins,Antigen Receptor, B-Cell,Antigen Receptors, B Cell,B Cell Antigen Receptor,B Cell Antigen Receptors,Bound Immunoglobulin, Membrane,Immunoglobulin, Membrane Bound,Immunoglobulin, Surface,Immunoglobulins, Membrane Bound,Membrane Bound Immunoglobulins,Receptor, B-Cell Antigen,Receptors, B-Cell Antigen
D011972	Receptor, Insulin	A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE.	Insulin Receptor,Insulin Receptor Protein-Tyrosine Kinase,Insulin Receptor alpha Subunit,Insulin Receptor beta Subunit,Insulin Receptor alpha Chain,Insulin Receptor beta Chain,Insulin-Dependent Tyrosine Protein Kinase,Receptors, Insulin,Insulin Receptor Protein Tyrosine Kinase,Insulin Receptors
D003600	Cytosol	Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.	Cytosols
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001402	B-Lymphocytes	Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.	B-Cells, Lymphocyte,B-Lymphocyte,Bursa-Dependent Lymphocytes,B Cells, Lymphocyte,B Lymphocyte,B Lymphocytes,B-Cell, Lymphocyte,Bursa Dependent Lymphocytes,Bursa-Dependent Lymphocyte,Lymphocyte B-Cell,Lymphocyte B-Cells,Lymphocyte, Bursa-Dependent,Lymphocytes, Bursa-Dependent
D014407	Tumor Cells, Cultured	Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.	Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured