Identification of a novel protein with GDP dissociation inhibitor activity for the ras-like proteins CDC42Hs and rac I.

We have recently cloned the human cDNA for a gene, denoted D4, that encodes a protein 67% identical to the bovine rhoGDI protein, a GDP dissociation inhibitor (GDI) for the ras-related rho-subtype proteins. We now present data on the cloning and structural analysis of the murine D4 cDNA and confirm its preferential expression in hematopoietic tissues. The predicted murine and human D4 proteins are almost 90% identical, indicating that D4 and rhoGDI are different genes and that they are probably members of a related family of genes. Functional studies with the human D4 protein demonstrate that D4 has GDI activity against the CDC42Hs and rac I proteins, but binds to these proteins with a significantly weaker affinity than does the rho-subtype GDI. These data suggest that D4, which will in subsequent communications be denoted as GDI.D4, might be a GDI for other known or as yet unidentified ras-like GTP-binding proteins. Alternatively, D4 could have other biochemical functions. During murine embryogenesis, D4 transcripts are detected in yolk-sac cells, where the earliest hematopoietic precursors are found. When these precursors undergo proliferation and differentiation in vitro, a dramatic increase in D4 expression is seen. D4 probably has a significant function during the growth and development of hematopoietic precursors.