p50RhoGAP

p50RhoGAP is a protein that belongs to the family of Rho GTPase-activating proteins (RhoGAPs). Named for its approximate 50 kilodalton molecular weight, it functions as a GTPase-activating protein toward members of the Rho family (RhoA, Rac1, Cdc42). By accelerating the intrinsic GTP hydrolysis of these GTPases, p50RhoGAP promotes the inactive GDP-bound state, thereby downregulating Rho signaling and modulating the actin cytoskeleton and related processes.

Most p50RhoGAPs contain a conserved RhoGAP domain that is sufficient for GAP activity. Additional regions can mediate interactions with membranes and signaling adaptors; the exact architecture varies between family members. The p50 designation refers to its typical apparent molecular weight on SDS-PAGE. Localization in the cell can be cytosolic or associated with membranes, depending on interacting partners and regulatory modifications.

Biological roles of p50RhoGAPs include regulation of cell shape, adhesion, and motility, as well as neuronal growth cone dynamics and neurite outgrowth. They act downstream of receptor signaling and other pathways, and their GAP activity is integrated with signaling inputs to fine-tune cytoskeletal remodeling. Activity and localization can be influenced by phosphorylation, lipid binding, and scaffold proteins, which help recruit the GAP to specific signaling complexes.

Regulation and interactions of p50RhoGAPs are often mediated by phosphorylation by kinases such as Src family members, as well as interactions with SH2- and SH3-domain–containing proteins and other adapters. These interactions help position p50RhoGAP within broader signaling networks that control Rho GTPase activity.

In research contexts, p50RhoGAPs are studied to understand the regulation of Rho GTPase signaling and cytoskeletal control. Changes in their expression or localization can affect cell motility and development in experimental systems.