Abstract
Dbl (B-cell lymphoma)-related guanine nucleotide exchange factors (GEFs), the largest family of GEFs, are directly responsible for the activation of Rho family GTPases and essential for a number of cellular events such as proliferation, differentiation and movement. The members of the Ephexin (Eph-interacting exchange protein) family, a subgroup of Dbl GEFs, initially were named for their interaction with Eph receptors and sequence homology with Ephexin1. Although the first Ephexin was identified about two decades ago, their functions in physiological and pathological contexts and regulatory mechanisms remained elusive until recently. Ephexins are now considered as GEFs that can activate Rho GTPases such as RhoA, Rac, Cdc42, and RhoG. Moreover, Ephexins have been shown to have pivotal roles in neural development, tumorigenesis, and efferocytosis. In this review, we discuss the known and proposed functions of Ephexins in physiological and pathological contexts, as well as their regulatory mechanisms.
Highlights
The Rho family of GTPases is a subgroup of the Ras superfamily
GTPase-activating proteins (GAPs) antagonize the function of guanine nucleotide exchange factors (GEFs) by stimulating Rho GTPases to hydrolyze bound GTP to GDP
GEF activity of Ephexins could be by Ephrin/Eph receptor-mediated receptor-mediated signaling, and diverse induced cellular processes induced
Summary
The Rho family of GTPases is a subgroup of the Ras superfamily. Like other small GTPases, the members of the Rho family function as molecular switches [1,2,3,4]. Rho GTPases are best known for their roles in the regulation of the actin cytoskeleton. They are involved in diverse cytoskeleton-dependent processes such as cell adhesion, cell motility, cytokinesis, phagocytosis, morphogenesis, and axon guidance [1,2,5]. The overall activity of a Rho GTPase in cells depends on its ratio of the GTP-bound to GDP-bound form. This ratio is controlled by its direct binding to GEFs, GAPs, or GDIs. GEFs activate. GAPs antagonize the function of GEFs by stimulating Rho GTPases to hydrolyze bound GTP to GDP.
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