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. Copyright (C) 2000 Federation of European Biochemical Societies.
Bibliographical noteFunding Information:
We are indebted to Dr. M.K. Brenner for critical reading of the manuscript, Dr. J. Camonis for giving us reagents necessary for the yeast two hybrid screens and Mr. Y. Markson for help with the figures. This work was supported by a grant from the Israel Science Foundation founded by the Israel Academy of Sciences and Humanities given to S.K.
- GDP/GTP exchange