A Review of Small GTPases

Small GTP-binding proteins (GTPases) serve to regulate a variety of cell signaling pathways and are therefore involved in a wide range of cell functions, processes, and morphology. The most studied small GTPase proteins are Ras, Rho, Rac, Cdc42, Rap, and Arf. They regulate molecular events by cycling between an inactive GDP-bound form and an active GTP-bound form. In their active (GTP-bound) state they bind to a specific binding domain to control downstream signaling cascades.

Many small GTPases are found in various isoforms; for example, Ras may be found as H-Ras, N-Ras, or K-Ras. Recent research has shown that isoforms of the same protein could have different functions. For example, one isoform could be involved in one signaling pathway, while another may be regulated in an entirely different pathway. Isoforms may even be implicated in different disease states.  For instance, mutations of the K-Ras gene have been shown to occur in a large percentage of pancreatic carcinomas. Since these isoforms have different functions, it’s important to have tools that can distinguish between them.

A wide variety of small GTPase assays are available, including many assays that specifically target small GTPase isoforms like K-Ras, Rac2 and RhoA. In addition, small GTPase expression vectors as well as a variety of retroviral and adenoviral vectors can help facilitate this important research area.