Rabbit Anti-Human PTK2 Polyclonal Antibody

Tibetan chicken, a unique plateau breed, has a suite of adaptive features that enable it to tolerate the high-altitude hypoxic environment. HIF-1 alpha (hypoxia inducible factor 1 subunit alpha) is a crucial mediator of the cellular response to hypoxia. HIF-1 alpha maintains oxygen homeostasis by inducing glycolysis, erythropoiesis, and angiogenesis. In this study, using ChIP-seq, we analyzed HIF-1 alpha binding regions in the chorioallantoic membrane (CAM) tissue of embryos, and identified differential HIF-1 alpha target genes (DTGs) by comparing Chahua (CH) and Tibetan chicken (TC) that had distinct genetic performances, associated with hypoxic adaptation. We identified 752 HIF-1 alpha target genes (TGs), of which 112 were DTGs between the two breeds. We found that eight genes (PTK2, GPNMB, CALD1, CBWD1, SLC25A1, SPRY2, NUPL2, and ST8SIA3) play important roles in hypoxic adaptation by regulating blood vessel development, energy metabolism through angiogenesis, vascular smooth muscle contraction, and various hypoxia-related signaling pathways (including VEGF and PI3K-Akt) in Tibetan chickens during embryonic development. This study enhances our understanding of the molecular mechanisms of hypoxic adaptation in Tibetan chickens and provides new insights into adaptation to hypoxia in humans and other species living at high altitude.

Activating mutations in GNAQ/GNA11, encoding GaqGproteins, are initiating oncogenic events in uveal melanoma (UM). However, there are no effective therapies for UM. Using an integrated bioinformatics pipeline, we found that PTK2, encoding focal adhesion kinase (FAK), represents a candidate synthetic lethal gene with GNAQ activation. We show that Gaq activates FAK through TRIO-RhoA non-canonical Gaq-signaling, and genetic ablation or pharmacological inhibition of FAK inhibits UM growth. Analysis of the FAK-regulated transcriptome demonstrated that GNAQ stimulates YAP through FAK. Dissection of the underlying mechanism revealed that FAK regulates YAP by tyrosine phosphorylation of MOB1, inhibiting core Hippo signaling. Our findings establish FAK as a potential therapeutic target for UM and other Gaq-driven pathophysiologies that involve unrestrained YAP function.