Isolation of the novel human guanine nucleotide exchange factor Src homology 3 domain-containing guanine nucleotide exchange factor (SGEF) and of C-terminal SGEF, an N-terminally truncated form of SGEF, the expression of which is regulated by androgen in prostate cancer cells.

In searching for androgen-responsive genes in human prostate cancer cells, we have isolated two cDNAs that encode alternate forms of a novel Src homology 3 domain-containing guanine nucleotide exchange factor (SGEF). The SGEF mRNA is widely expressed in human tissues, and the predicted 871-amino acid SGEF protein contains Dbl homology and pleckstrin homology domains as well as an N-terminal proline-rich domain, a C-terminal Src homology 3 domain, and two nuclear localization signals. The second cDNA encodes a 139-amino acid N-terminally truncated form of SGEF designated C-terminal SGEF (CSGEF). In contrast to SGEF, CSGEF mRNA expression is restricted to prostate and liver. Moreover, CSGEF expression is up-regulated by androgens in LNCaP cells, whereas that of SGEF is not. Up-regulation of CSGEF was sensitive to actinomycin D but did not require new protein synthesis. The SGEF gene is located on chromosome 3q25.2 and consists of at least 15 exons. Based on the structure of the SGEF and CSGEF cDNAs, we deduced that CSGEF expression is controlled by an alternate androgen-responsive promoter of the SGEF gene. We hypothesize that SGEF is a ubiquitous regulator of Rho guanosine triphosphatases, whereas CSGEF may function as an androgen-induced regulator of Rho guanosine triphosphatase activity in epithelial cells of the human prostate.