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GTPase Activating Proteins

1993; Springer Science+Business Media; Linguagem: Inglês

10.1007/978-3-642-78267-1_23

1865-0325

Frank McCormick,

Cellular transport and secretion

Small GTPases such as ras p21 have low intrinsic GTPase activity and depend on GTPase activating proteins (GAPs) to convent their active GTP-bound forms to their inactive GDP-bound counterparts (Bollag and McCormick 1991b). GAPs therefore appear to be major negative regulators of these GTPases (Fig. 1). In addition, we and others have proposed the possibility that GAP-mediated down-regulation may be coupled to signal output so that GAPs comprise part of small GTPase effector systems (Adari et al. 1988; Calés et al. 1988; McCormick 1989; Hall 1990). This proposal is based mainly on the fact that GAPs interact only with the GTP-bound forms of ras p21 proteins (a criterion for a ras effector), and that GAPs bind ras p21 proteins at or near the so-called effector-binding site. The hypothesis has gained support from the recent observation that certain effectors of heterotrimeric G-proteins are also GAPs for these proteins (Berstein et al. 1992; Arshavsky et al. 1992), but remains controversial for small GTPases such as ras p21. In addition to the major issue of a possible role in effector functions for GAPs, a number of fundamental questions relating to their function have yet to be solved. For example, we have very little idea how, at the molecular level, GAPs stimulate GTPase activity or how GAP activities are regulated in cells. In this chapter, we will discuss known properties of GAPs for ras p21 and related proteins and speculate about their possible functions.