Article

Choose your own path: specificity in Ras GTPase signaling.

Department of Medicine, Division of Rheumatology, University of California, San Diego, CA 92093-0726, USA.
Molecular BioSystems (impact factor: 3.53). 05/2008; 4(4):293-9. DOI:10.1039/b716887j pp.293-9
Source: PubMed

ABSTRACT The Ras superfamily of small G proteins contributes importantly to numerous cellular and physiological processes (M. F. Olsen and R. Marais, Semin. Immunol., 2000, 12, 63). This family comprises a large class of proteins (more than 150) which all share a common enzymatic function: hydrolysis of the gamma-phosphate of guanosine triphosphate (GTP) to create the products guanosine diphosphate (GDP) and inorganic phosphate (Y. Takai, T. Sasaki and T. Matozaki, Physiol. Rev., 2001, 81, 153). For this reason Ras family proteins, which include the Ras, Rho, Arf/Sara, Ran and Rab subfamilies, are classified as GTPases (G. W. Reuther and C. J. Der, Curr. Opin. Cell Biol., 2000, 12, 157). Guanine nucleotide coupling is a key regulator of enzymatic function; thus, Ras family GTPases participate in signal transduction. Ras signaling depends on binding to effectors. Many of the known effectors can bind to multiple Ras isotypes, often leading to common cellular outcomes, but each Ras isotype also engages specific effector pathways to mediate unique functions. Further, each Ras isotype can propagate multiple signaling pathways, indicating the presence of cellular determinants which allow for promiscuity in Ras-effector interactions while also maintaining specificity. Small distinctions in sequence, structure, and/or cellular regulation contribute to these differences in Ras-effector binding and subsequent cellular effects. A major focus of investigation in the Ras signaling field is identifying the determinants of these individualized functions. This review will attempt to summarize the current state of understanding of this question (with a particular focus on the Ras subfamily) and the approaches being taken to address it, and will discuss prospective areas for future investigation.

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Keywords

cellular regulation
 
common cellular outcomes
 
current state
 
F. Olsen
 
future investigation
 
Guanine nucleotide coupling
 
guanosine triphosphate
 
known effectors
 
major focus
 
multiple Ras isotypes
 
numerous cellular
 
particular focus
 
products guanosine diphosphate
 
Ras-effector binding
 
Ras-effector interactions
 
reason Ras family proteins
 
Small distinctions
 
specific effector pathways
 
subsequent cellular effects
 
T. Matozaki
 

Lawrence E Goldfinger