{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n G-protein–coupled receptor kinase–interacting protein 2 (GIT2) is an ubiquitously expressed, multidomain ARF GTPase–activating protein that, through alternative splicing, produces several isoforms with distinct functional properties. GIT2 plays key roles in regulating membrane trafficking and receptor internalization via its ARF GAP activity and in coordinating cytoskeletal reorganization and focal adhesion turnover, thereby controlling directional cell migration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In immune cells, GIT2 is essential for precise chemotactic responses. In neutrophils, it not only ensures accurate directional sensing and orientation of superoxide production but also suppresses excessive reactive oxygen species generation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Similarly, in thymocytes, loss of GIT2 leads to enhanced Rac activation and altered actin polymerization that compromise effective scanning within the thymic cortex."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, GIT2 participates in the regulation of immune synapse–mediated signaling. At the immunological synapse of regulatory T cells, GIT2 associates with components of a focal adhesion complex to couple CTLA-4–dependent signals with downstream effectors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n GIT2 is also implicated in the DNA damage response; it becomes phosphorylated by ATM kinase and is recruited to sites of double-strand breaks, contributing to the stabilization of repair complexes and maintenance of genomic integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In inflammatory signaling, GIT2 functions as a negative regulator. By recruiting deubiquitinating enzymes to terminate Toll-like receptor–induced NF-κB and MAPK activation, GIT2 dampens the ubiquitination of TRAF6 and limits proinflammatory cytokine production."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, in vivo studies indicate that disruption of GIT2 function leads to a spectrum of physiological abnormalities. For example, GIT2 knockout mice exhibit anxiety-like behaviors, highlighting its role not only in mediating cellular signaling and cytoskeletal dynamics but also in maintaining organismal homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore GIT2 as a multifunctional scaffold and regulatory protein that orchestrates key signaling pathways involved in membrane trafficking, cell migration, immune regulation, and genomic stability.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "R T Premont, A Claing, N Vitale, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The GIT family of ADP-ribosylation factor GTPase-activating proteins. 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