Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The oncogenic protein Vav harbours a complex array of structural motifs, including leucine-rich, Dbl-homology, pleckstrin-homology, zinc-finger, SH2 and SH3 domains. Upon stimulation by antigens or mitogens, Vav becomes phosphorylated on key tyrosine residues and associates with other signalling proteins, including the mitogen receptors Zap-70 (ref. 6), Vap-1 (ref. 5) and Slp-76 (ref. 7). Disruption of the vav locus by homologous recombination causes severe defects in signalling by primary antigen receptors, leading to abnormal lymphocyte proliferation and lymphopenia. Despite the importance of Vav cell signalling, the function of this protein remains unknown. Here we show that tyrosine-phosphorylated Vav, but not the non-phosphorylated protein, catalyses GDP/GTP exchange on Rac-1, a protein implicated in cell proliferation and cytoskeletal organization, causing this GTPase to switch from its inactive to its active state. Transfection experiments also show that phosphorylation of Vav on tyrosine residues leads to nucleotide exchange on Rac-1 in vivo and stimulates c-Jun kinase, a downstream element in the signalling pathway involving this GTPase. Our results have identified a function for Vav and define a mechanism in which engaged membrane receptors activate its signalling pathway.
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PMID:Phosphotyrosine-dependent activation of Rac-1 GDP/GTP exchange by the vav proto-oncogene product. 899 Jan 21

Lyp controls lymphopenia and T-cell mediated autoimmune diabetes in the BioBreeding (BB) rat possibly by interacting with T-cell maturation in the thymus. The protooncogene vav (p95) is involved in T-cell activation and in the intrathymic selection of developing T cells. We have previously reported increased production of IFN-gamma of self reactive thymocytes in the thymus medulla of Lyp/Lyp BB rats. Lymphopenia and diabetes may therefore be linked to an increase in thymocyte activation leading to a bias in thymocyte development. The purpose of this study was therefore to investigate whether the expression of p95"a" in primary lymphoid tissues from congenic Lyp/Lyp, Lyp/+ and +/+ BB rats was correlated to the Lyp genotype using in situ hybridization and reverse transcription (RT)-PCR. It was found that the expression of vav mRNA in the thymus was increased in Lyp/Lyp compared to Lyp/+ and +/+ rats (p < 0.05). Western blot analysis revealed that the amount of p95 vav protein in Lyp/Lyp thymus was also increased. The results show that vav expression correlates with the lymphopenia phenotype and diabetes development in congenic Lyp/Lyp BB rats. An increase in the availability of p95vav during the development and activation of thymocytes in Lyp/Lyp BB rats may therefore contribute to the generation of islet autoreactivity, lymphopenia or both.
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PMID:Differential expression of p95vav in primary lymphoid tissue of BB rats congenic for the lymphopenia gene. 1043 93