Small GTP-Binding Proteins

Abstract

Small GTP-binding proteins (G proteins) exist in eukaryotes from yeast to human and constitute a superfamily consisting of more than 100 members. This superfamily is structurally classified into at least five families: the Ras, Rho, Rab, Sar1/Arf, and Ran families. They regulate a wide variety of cell functions as biological timers (biotimers) that initiate and terminate specific cell functions and determine the periods of time for the continuation of the specific cell functions. They furthermore play key roles in not only temporal but also spatial determination of specific cell functions. The Ras family regulates gene expression, the Rho family regulates cytoskeletal reorganization and gene expression, the Rab and Sar1/Arf families regulate vesicle trafficking, and the Ran family regulates nucleocytoplasmic transport and microtubule organization. Many upstream regulators and downstream effectors of small G proteins have been isolated, and their modes of activation and action have gradually been elucidated. Cascades and cross-talks of small G proteins have also been clarified. In this review, functions of small G proteins and their modes of activation and action are described.

The Ras-related protein AGS1/RASD1 suppresses cell growth

“…Keywords: AGS1; RASD1; Dexras1; G-protein; apoptosis; cancer AGS1/RASD1 is a member of the Ras superfamily of small G-proteins and is most similar to the Ras subgroup involved in cell growth, differentiation and transformation (Kemppainen and Behrend, 1998;Cismowski et al, 1999;Takai et al, 2001). AGS1/RASD1 and a related Ras-family member Rhes/TEM2 (RASD2), which exhibits 60% amino-acid sequence identity with AGS1/RASD1, apparently define a distinct subgroup within the larger Ras group of proteins.…”

Small GTPase protein Rac-1 is activated with maturation and regulates cell morphology and function in chondrocytes

“…In addition, Rho GTPases are involved in other cellular functions, including gene expression, cell cycle progression, and enzymatic regulation. [13][14][15] Recent work has pointed to the relevance and potential importance of Rho GTPases in chondrocyte function. In gain-of-function experiments using the chondrogenic cell line ATDC5, RhoA over-expression was found to induce actin filament organization and stress fibers, to increase proliferation and proteoglycan production, and to suppress maturation and hypertrophy.…”

BCR/ABL and IL-3 activate Rap1 to stimulate the B-Raf/MEK/Erk and Akt signaling pathways and to regulate proliferation, apoptosis, and adhesion

“…Thus, members of the STAT family of latent transcription factors, mainly STAT5, are recruited to the cytokine receptors through its SH2 domain to become phosphorylated and activated by Jak2. The small GTPase Ras, which is inactive in the GDP-bound form, is also activated by the exchange of GDP for GTP, a reaction which is catalysed by guanine nucleotide exchange factors (GEFs) recruited to the activated cytokine receptors (Bar-Sagi and Hall, 2000;Takai et al, 2001). The activated GTP-bound form of Ras then activates the Raf-1/MEK/Erk signaling cascade leading to proliferation of cells.…”