The Ras guanine nucleotide exchange factor (RGEF) functions as a positive regulator of Ras activity. With the purification of a novel RGEF, p55 from bovine brains, we have performed the molecular cloning of the gene encoding p55. A full length cDNA clone of 3.0 kb was obtained by screening bovine brain cDNA library and its nucleotide sequence was determined. The deduced primary amino acid sequences of p55 cDNA showed a marked homology with several domains of C. elegans unc-33 gene, but had no significant homology with mSOS or Ras-GRF (CDC25 mM), known members of RGEF family. Moreover, p55 transcripts were detected in bovine brains but not other tissues, suggesting the specific expression of p55 in brain tissues. As demonstrated by genetic studies, C. elegans unc-33 is responsible for the regulation of outgrowth and guidance of neuron axons. Thus, our results raise the possibility that p55 might be a novel type of RGEF participating in the neuronal activity. In a separate approach, we examined the physiological role of mSOS in signal transduction of T-cell antigen receptor (TCR). The interaction between mSOS and Src family tyrosine protei kinases (TPKs) (Fyn and Lck) or Syk family TPK (Zap-70) has been investigated. We found that stimulation of TCR induced the activation of mSOS, and that Fyn TPK, but not Lck or Zap-70 TPK, regulated mSOS, bound to GRB2, through tyrosine phosphorylation of Shc. This provided a new insight into the mechanism of TCR signal transduction which involves TPKs and Ras.
