Signal Transmission via Ras Proteins

Intracellular signal transduction employs central switching stations that receive, modulate and transmit signals further. The Ras proteins (also known as p2T proteins) make up a switching station of particular importance for growth and differentiation processes. The Ras proteins process signals received by receptor tyrosine kinases, by receptors with associated tyrosine kinase activity and by G-protein-coupled receptors, and transmit these into the cell interior (Fig. 9.1). 

The general importance of Ras proteins in growth regulation was recognized at the beginning of the 1980s, when it was demonstrated that close to 30 % of all solid tumors in humans show a mutation in the Ras gene. 

Following the discovery of the Ras protein, it was quickly estabhshed that Ras proteins are a family within a large superfamily, known today as the Ras superfamily of monomeric GTPases. Hie members of the superfamUy of Ras proteins are regulatory GTPases of 16-25 kDa, which are active as monomers. 

Within the Ras superfamUy, at least five subfamilies can be differentiated (Boguski and McCormick, 1993 and Table 9.1). Hiese are the Ras/Rap, the Rho/Rac, the Rab, Ran and zlr/subfamUies. 

The lifetime of the active GTP-bound state may be reduced by regulatory GTPase activating proteins. The primary fimction of the GTPase activating proteins (GAP) is to negatively regulate the Ras proteins and Ras-related proteins. 

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