Identification of the protein encoded by the human diffuse B-cell lymphoma (dbl) oncogene.

Abstract

The dbl oncogene was initially isolated from a human diffuse B-cell lymphoma. Antisera from mice bearing tumors induced by this oncogene specifically detected a protein of about 66 kDa (p66) in dbl transformants. dbl cDNA-selected poly(A)I RNA isolated from a transfectant clone expressing p66 directed the in vitro synthesis of this protein, establishing that it is encoded by dbl. Subcellulat localization studies revealed that p66 is a cytoplasmic protein distributed between cytosol and crude membrane fractions. Moreover, p66 was shown to be a phosphoprotein, with phosphorylation specific to serine residues. Our characterization of the dbl-encoded protein appears to distinguish this transforming gene product from those of other known oncogenes.

A RHO GTPase-mediated pathway is required during P cell migration in Caenorhabditis elegans

“…Rho family member proteins may need to cycle between GDP-and GTP-bound forms to achieve maximal activity. This has been proposed as an explanation for the observation that constitutively active Rho family members are only weak oncogenes (1), whereas endogenous RHO activated by exchange factors like Dbl can be potent (40,41). It is also possible that Rho-1 may have a higher intrinsic GTPase activity that reduces the effectiveness of the G14V mutation.…”

Tyrosine Phosphorylation of Dbl Regulates GTPase Signaling

“…Dbl was initially discovered as a potent fibroblast transforming sequence, the activity of which is stimulated upon truncation of the amino terminus of the protein (1,7,9,25). Dbl has been shown to activate RhoA, Rac1, and Cdc42 and to be expressed in the central nervous system, testis, as well as in neuroectodermal cancers and Ewing sarcomas (21)(22)(23)(24).…”

“…Dbl was the first identified mammalian GEF and as such is considered to be the prototypic member of the family (1). Two highly conserved domains characterize Dbl family GEFs: a unique Dbl homology domain and a pleckstrin homology domain.…”

RhoG Signals in Parallel with Rac1 and Cdc42

“…Vav1 and Vav2 are two highly related GEFs for Rac and Cdc42 (26,32), and both bound strongly to RhoG and a DH-PH fragment of Vav2 efficiently stimulated guanine nucleotide exchange in vitro. The related RhoA and Cdc42 GEFs, Dbl and Dbs (28,39), both bound weakly to nucleotide-free RhoG, but only Dbs stimulated guanine nucleotide exchange activity on RhoG in vitro. Ect2 has been described as a RhoA and Rac-specific GEF (40) and it also bound weakly to nucleotide-free RhoG.…”