Purified Mouse Anti-GIT1

Activation of adrenergic receptors (AR), such as β2AR leads to activation of  heterotrimeric G proteins and recruitment of G protein-coupled receptor kinases (GRKs). Phosphorylation of the activated receptor by GRKs promotes the binding of arrestin protein which prevents further G protein activation. GRK interactor 1 (GIT1) was identified in a yeast two-hybrid screen for proteins that bind GRK2. GIT1 has an N-terminal Zn2+ finger-like motif involved in GTPase activating activity and multipe ankyrin repeat units. In vitro, GIT1 is a GTPase-activating protein (GAP) for the ADP ribosylation factor (ARF) family of small GTP-binding proteins. In rat, GIT1 is widely expressed with the highest levels in the testis and lowest levels in the liver and spleen. Overexpression of GIT1 in HEK293 cells causes reduced β2AR signaling and increased receptor phosphorylation as a result of reduced receptor internalization and resensitization. In addition, GIT1 interacts directly with paxillin and the PIX exchange factors, and indirectly with PAKs, Rac1, and Nck. GIT proteins are also now known to be PIP3-stimulated GAPs for ARF6. Thus, GIT1 activation of ARF proteins may involve cell signaling pathways that are important for endocytosis, cell adhesion, and cytoskeletal dynamics.