Rho guanine nucleotide exchange factors: regulators of Rho GTPase activity in development and disease

被引:284
作者
Cook, D. R. [1 ]
Rossman, K. L. [2 ,3 ]
Der, C. J. [2 ,3 ]
机构
[1] Univ N Carolina, Div Chem Biol & Med Chem, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
[2] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA
[3] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
关键词
Rac1; RhoA; Cdc42; guanine nucleotide exchange factors; cancer; mouse models; EXPRESSION CDNA CLONING; LINKED MENTAL-RETARDATION; SIGNAL TRANSDUCER VAV1; CELL LYMPHOMA INVASION; RAC ACTIVATOR TIAM1; METASTASIS; TIAM2; PROTEIN-KINASE-C; B-CELL; PROSTATE-CANCER; T-CELL;
D O I
10.1038/onc.2013.362
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The aberrant activity of Ras homologous (Rho) family small GTPases (20 human members) has been implicated in cancer and other human diseases. However, in contrast to the direct mutational activation of Ras found in cancer and developmental disorders, Rho GTPases are activated most commonly in disease by indirect mechanisms. One prevalent mechanism involves aberrant Rho activation via the deregulated expression and/or activity of Rho family guanine nucleotide exchange factors (RhoGEFs). RhoGEFs promote formation of the active GTP-bound state of Rho GTPases. The largest family of RhoGEFs is comprised of the Dbl family RhoGEFs with 70 human members. The multitude of RhoGEFs that activate a single Rho GTPase reflects the very specific role of each RhoGEF in controlling distinct signaling mechanisms involved in Rho activation. In this review, we summarize the role of Dbl RhoGEFs in development and disease, with a focus on Ect2 (epithelial cell transforming squence 2), Tiam1 (T-cell lymphoma invasion and metastasis 1), Vav and P-Rex1/2 (PtdIns(3,4,5) P3 (phosphatidylinositol (3,4,5)-triphosphate)-dependent Rac exchanger).
引用
收藏
页码:4021 / 4035
页数:15
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