Disease relevance of GIT2

• The Cat2 transcript increased in response to osmotic stress, but was repressed by dehydration [1].
• Marked eosinophilia, associated with up-regulation of eotaxin-1, was present in the bronchoalveolar lavage fluid of 3-week-old CAT2-deficient mice [2].

High impact information on GIT2

• Another ArfGAP, Git2, was found to be a component of the Gbetagamma-mediated directional sensing machinery, while simultaneously playing an essential role in the suppressive control of superoxide production, which is mediated by vesicle transport in GPCR-stimulated neutrophils [3].
• However, it is not clear whether GITs function to activate or repress motility or if the predominant GIT forms, GIT1 and GIT2, serve distinct or redundant roles [4].
• GIT2 represses Crk- and Rac1-regulated cell spreading and Cdc42-mediated focal adhesion turnover [4].
• Finally, we show that loss of GIT2 is sufficient to induce migration of the nontransformed epithelial cell line MCF10A [4].
• These results suggest that inactivation of GIT2 function is a required step for induction of cell motility and that GIT2 may be a target of oncogenic signaling pathways that regulate cell migration [4].

Biological context of GIT2

• GIT2 undergoes extensive alternative splicing and exists in at least 10 and potentially as many as 33 distinct forms [5].
• Unlike ARF-GAP1, GIT1 and GIT2 stimulate hydrolysis of GTP bound to ARF6 [6].

Anatomical context of GIT2

• Thus, our data suggest that CAT2 regulates anti-inflammatory processes in the lungs via regulation of dendritic cell activation and subsequent T cell responses [2].
• Despite the presence of activated alveolar macrophages in CAT2-deficient mice, NO production was compromised in these cells [2].

Physical interactions of GIT2

• On the other hand, paxillin localization to focal complexes at the cell periphery was unaffected or even augmented by Git2-short overexpression [7].

Regulatory relationships of GIT2

• The GIT family of ADP-ribosylation factor GTPase-activating proteins. Functional diversity of GIT2 through alternative splicing [5].

Other interactions of GIT2

• The longest form of GIT2 is colinear with GIT1 and shares the same domain structure, whereas one major splice variant prominent in immune tissues completely lacks the carboxyl-terminal domain [5].
• Perinuclear localization of paxillin, which was sensitive to ARF inactivation, was also affected by Git2-short overexpression [7].
• An ADP-ribosylation factor GTPase-activating protein Git2-short/KIAA0148 is involved in subcellular localization of paxillin and actin cytoskeletal organization [7].
• Here we demonstrate an obligatory role for endogenous GIT2 in repression of lamellipodial extension and FA turnover by Rac1- and Cdc42-dependent signaling pathways, respectively [4].
• Unlike paxillin, however, Git2-short did not accumulate at focal adhesions underneath the cell [7].

References