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

Abstract

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.

Toxicogenomics of Kojic Acid on Gene Expression Profiling of A375 Human Malignant Melanoma Cells

“…64,65) Moreover, a novel putative human Rho GEF designated Src homology 3 (SH3) domain-containing guanine nucleotide exchange factor (SGEF) provides a direct link for cross-talk between the androgen receptor and Rho GTPase signaling pathways in prostate cancer cells. 66) In consequence, the down-regulated ARHGEF16 gene by kojic acid may suppress or deactivate the tumor progression of A375 melanoma cancer cells.…”

SGEF, a RhoG Guanine Nucleotide Exchange Factor that Stimulates Macropinocytosis

“…Functionally, both Trio and Kalirin are implicated as a catalyst for RhoG activation during neurite outgrowth (Blangy et al, 2000;May et al, 2002). SGEF mRNA was detected in brain extracts (Qi et al, 2003), providing the possibility that a similar function(s) exists for SGEF. At the same time, the expression of SGEF in hematopoietic cell lines is noteworthy when considering that RhoG regulates gene transcription in B and T cells and homozygous disruption of the RhoG gene in mice results in elevated levels of immunoglobulins in serum and a mild increase in lymphocyte response to antigen (Vigorito et al, 2004).…”

“…SGEF (SH3-containing Guanine Nucleotide Exchange Factor) was initially found in a screen for androgen-responsive genes in human prostate (Qi et al, 2003). Two alternatively transcribed forms of SGEF gene were isolated, one which encodes the full-length molecule of 871 amino acids and the other an androgen-inducible splice-variant of 139 amino acids that contains only a small segment of the pleckstrin homology (PH) domain and the entire carboxyl Src homology 3 (SH3) domain.…”

Salmonella : from Pathogenesis to Therapeutics

“…Next, they investigated how SopB activates RhoG and discovered that SGEF (SH3-containing guanine nucleotide exchange factor) was recruited to ruffles in a SopB-dependent manner and that it was required for SopB-dependent RhoG activation. SGEF is a recently identified RhoG exchange factor that stimulates macropinocytosis (8,42). They also demonstrated that, while not involved in invasion, SopB activation of Cdc42 modulates nuclear responses to serovar Typhimurium infection.…”