English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

Vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptors are implicated in development and tumorigenesis and dual inhibitors like sunitinib are prescribed for cancer treatment. While mammalian VEGF and PDGF receptors are present in multiple isoforms and heterodimers,Drosophila encodes one ancestral PDGF/VEGF receptor, PVR. We identified PVR in an unbiased cell-based RNA interference (RNAi) screen of allDrosophila kinases and phosphatases for novel regulators of TORC1. PVR is essential to sustain target of rapamycin complex 1 (TORC1) and extracellular signal-regulated kinase (ERK) activity in cultured insect cells and for maximal stimulation by insulin. CG32406 (henceforth, PVRAP, forPVR a daptorp rotein), an Src homology 2 (SH2) domain-containing protein, binds PVR and is required for TORC1 activation. TORC1 activation by PVR involves Tsc1/Tsc2 and, in a cell-type-dependent manner, Lobe (ortholog of PRAS40). PVR is required for cell survivalin vitro , and both PVR and TORC1 are necessary for hemocyte expansionin vivo . Constitutive PVR activation induces tumor-like structures that exhibit high TORC1 activity. Like its mammalian orthologs, PVR is inhibited by sunitinib, and sunitinib treatment phenocopies PVR loss in hemocytes. Sunitinib inhibits TORC1 in insect cells, and sunitinib-mediated TORC1 inhibition requires an intact Tsc1/Tsc2 complex. Sunitinib similarly inhibited TORC1 in human endothelial cells in a Tsc1/Tsc2-dependent manner. Our findings provide insight into the mechanism of action of PVR and may have implications for understanding sunitinib sensitivity and resistance in tumors.

molecular and cellular biology

Platelet-Derived Growth Factor/Vascular Endothelial Growth Factor Receptor Inactivation by Sunitinib Results in Tsc1/Tsc2-Dependent Inhibition of TORC1