Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Localization of DEF6 (SLAT/IBP), a Rho-family guanine nucleotide exchange factor, to the center of the immune synapse is dependent upon ITK, a Tec-family kinase that regulates the spatiotemporal organization of components of T cell signaling pathways and Cdc42-dependent actin polymerization. Here we demonstrate that ITK both interacts with DEF6 and phosphorylates DEF6 at tyrosine residues Tyr(210) and Tyr(222). Expression of a GFP-tagged Y210E-Y222E phosphomimic resulted in the formation of DEF6 cytoplasmic granules that co-localized with decapping enzyme 1 (DCP1), a marker of P-bodies; sites of mRNA degradation. Similarly treatment of cells with puromycin or sodium arsenite, reagents that arrest translation, also resulted in the accumulation of DEF6 in cytoplasmic granules. Bioinformatics analysis identified a glutamine-rich, heptad-repeat region; a feature of aggregating proteins, within the C-terminal region of DEF6 with the potential to promote granule formation through a phosphorylation-dependent unmasking of this region. These data suggest that in addition to its role as a GEF, DEF6 may also function in regulating mRNA translation.
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PMID:DEF6, a novel substrate for the Tec kinase ITK, contains a glutamine-rich aggregation-prone region and forms cytoplasmic granules that co-localize with P-bodies. 2282 99

Kidney renal clear cell carcinoma (KIRC) is one of the most common cancers globally, with an overall poor prognosis. The Janus kinase (JAK) family plays an essential role in cellular mechanisms such as proliferation, metastasis, invasion, and immunity. In our study, various web-portals were used to explore the expression and clinical significance of JAK3 in KIRC. JAK3 expression was significantly up-regulated in KIRC tissues. Patients with KIRC having high JAK3 levels displayed a substantially decreased disease-free survival rate and overall survival rate. Significant correlations were obtained between JAK3 expression and the abundance of immune cells and immune biomarker sets. Enrichment function analysis revealed that gene function significantly correlated with JAK3, which was primarily associated with the immune response, JAK-STAT signaling pathway, Ras signaling pathway via several cancer-related kinases, miRNAs, and transcription factors. Moreover, we also identified several kinase, miRNA or transcription factor targets of JAK3 in KIRC. The hub genes (JAK3, FCHO1, INSl3, DEF6, and GPR132) were associated with the activation or inhibition of several famous cancer related pathways. Our results demonstrated that JAK3 is a potential biomarker and associated with immune infiltration in KIRC.
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PMID:JAK3 is a potential biomarker and associated with immune infiltration in kidney renal clear cell carcinoma. 3257 38