background:
Heterotrimeric G protein-mediated signal transduction is a dynamically regulated process with the intensity of signal decreasing over time despite the continued presence of the agonist (1,2). G protein-coupled receptor kinases (GRKs) are activated by activated G protein-coupled receptors, and they function to phosphorylate and inactivate cell surface receptors in the heterotrimeric G protein signaling cascade (3,4). GIT1 (for GRK-interactor 1) and GIT2 are GTPase-activating proteins (GAP) for members of the ADP ribosylation factor (ARF) family of small GTP-binding proteins, which are involved in vesicular trafficking (5,6). GIT1 overexpression results in reduced internalization and resensitization of b2-adrenergic receptor, thus reducing b2-adrenergic receptor signaling (5).
Function:
GTPase-activating protein for the ADP ribosylation factor family. May serve as a scaffold to bring together molecules to form signaling modules controlling vesicle trafficking, adhesion and cytoskeletal organization. Increases the speed of cell migration, as well as the size and rate of formation of protrusions, possibly by targeting PAK1 to adhesions and the leading edge of lamellipodia. Sequesters inactive non-tyrosine-phosphorylated paxillin in cytoplasmic complexes.
Subcellular Location:
Cytoplasm. Cycles between at least 3 distinct intracellular compartments, including focal adhesions, cytoplasmic complexes and membrane protrusions. During cell migration, when cells detach, moves from the adhesions into the cytoplasmic complexes towards the leading edge, while, when cells adhere, it is found in vinculin-containing adhesions. Recruitment to adhesions may be mediated by active tyrosine-phosphorylated paxillin.
Post-translational modifications:
Phosphorylated on tyrosine residues by PTK2 and SRC in growing fibroblasts. Tyrosine-phosphorylation is increased following cell spreading on fibronectin, decreased in cells arrested in mitosis and increased in the ensuing G1 phase.
Similarity:
Contains 3 ANK repeats.
Contains 1 Arf-GAP domain.
Database links:
Entrez Gene: 28964 Human
Entrez Gene: 216963 Mouse
Entrez Gene: 83709 Rat
Omim: 608434 Human
SwissProt: Q9Y2X7 Human
SwissProt: Q68FF6 Mouse
SwissProt: Q9Z272 Rat
Unigene: 514051 Human
Unigene: 290182 Mouse
Unigene: 34521 Rat
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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