Vav, a GDP/GTP nucleotide exchange factor, interacts with GDIs, proteins that inhibit GDP/GTP dissociation.
Vav functions as a specific GDP/GTP nucleotide exchange factor which is regulated by tyrosine phosphorylation in the hematopoietic system. Loss of the amino-terminus sequences of Vav was sufficient to control its transforming potential and its function in T cells. We report here the identification of the hematopoietic GDP dissociation inhibitor protein, Ly-GDI, as a protein that interacts with the amino-terminus of Vav. Further analysis confirmed that Vav and Ly-GDI interact both in in vitro and in in vivo assays. This association is maximal only when the amino region of Vav is intact and requires an intact carboxy-terminus of Ly-GDI. The interaction between Vav and Ly-GDI is not dependent on the tyrosine phosphorylation status of Vav. In addition, Rho-GDI, the highly homologous protein to Ly-GDI, associates with Vav as well. The contribution of the interaction between Vav and GDIs, proteins that are involved in the GDP/GTP exchange processes, to the biological function of Vav is further discussed.
Groysman
M
M
The Hubert H. Humphrey center for Experimental Medicine and Cancer Research, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Russek
C S
CS
Katzav
S
S
D000818:Animals; D018797:Cell Cycle Proteins; D002460:Cell Line; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006801:Humans; D051379:Mice; D015778:Minor Histocompatibility Antigens; D008970:Molecular Weight; D016853:Muromonab-CD3 / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding / Q000187:drug effects; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051567:Proto-Oncogene Proteins c-vav; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D014162:Transfection; D025521:Tumor Suppressor Proteins; D020798:Two-Hybrid System Techniques; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
C569658:ARHGDIB protein, human; C569659:Arhgdib protein, mouse; D018797:Cell Cycle Proteins; D020730:Guanine Nucleotide Dissociation Inhibitors; D015778:Minor Histocompatibility Antigens; D016853:Muromonab-CD3; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins; C496618:VAV1 protein, human; C496619:Vav1 protein, mouse; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; D006153:Guanosine Diphosphate; D019000:Phosphotyrosine; D006160:Guanosine Triphosphate