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In this first X chromosome-wide association study of adult patients with IBD, we identified an IBD susceptibility locus with genome-wide significance at rs2427870 on chrXq26.3, located 66 kbp upstream of CD40LG and 83.4 kbp upstream of ARHGEF6 [OR, 1.22; combined p = 3.79 x 10-15].
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we discuss recent findings in key physiological systems that exemplify current understanding of the function of this important regulatory complex. Further, we draw attention to gaps in crucial information that remain to be filled to allow a better understanding of the many roles of the GIT-PIX complex in health and disease
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show that ARHGEF6 is constitutively linked to GIT1, a GAP of Arf family small G proteins, and that ARHGEF6 phosphorylation enables binding of the 14-3-3 adaptor protein to the ARHGEF6/GIT1 complex
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The novel recycling regulator alpha-PIX and the degradation factor c-Cbl closely cooperate in the regulation of EGFR trafficking.
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c-Cbl negatively regulates alphaPix-mediated cell migration and invasion; the lack of c-Cbl in C6 and A172 glioma cells is responsible for their malignant behavior
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results suggest that low doses of chlorambucil and very low doses of chronic oxidative stress together kill Cbl-resistant ovarian carcinoma cells and ARHGEF6 signaling may have an instrumental role in induction of apoptosis in Cbl(cos) cells.
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These findings suggest that alpha Pix plays an important role in mutant huntingtin aggregation.
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The interaction of alphaPix with CagA activates PAK1, ERK and NF-kappaB, which induces IL-8 expression in H. pylori-infected gastric epithelial cells.
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The plexin-B1/Rac interaction inhibits PAK activation and enhances Sema4D ligand binding
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Expression of Cbl-b effectively blocks the ability of Cool-2 to stimulate PAK, providing an additional mechanism, aside from catalyzing receptor ubiquitination, by which Cbl-b acts as a negative regulator for signaling activities requiring PAK activation.
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Data suggest that Rac-dependent activation of the NFkappaB pathway may be a critical element promoting thrombin-induced tissue factor expression and activity, and thus a prothrombotic state in pulmonary hypertension.
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Whereas alphaPIX guanine nucleotide exchange factor activity contributes to enhanced formation of cellular protrusions, the GEF-independent association with calpain 4 leads to induction of a yet unknown signaling cascade resulting in cell spreading.
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Semi-quantitative RT-PCR experiments with 6 of those genes confirmed higher expression of DNCH2, ARHGEF6, NPM1 and SRI and lower expression of NRGN and TM4SF2 in GBM tumors.
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PAK4 and alphaPIX can induce highly localized changes in actin dynamics and thereby regulate size and number of podosomes in primary human macrophages.
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phosphorylation of CagA induces the dephosphorylation of alpha-Pix, which may modulate cytoskeletal changes of gastric epithelial cells through PAK