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pharmacology and binding assay analysis Module 4 - New dimensions of activity: Allosteric modulators and kinetics

new antifibrotic cGAS/STING signaling pathway that suppresses pathological angiogenesis in liver and kidney We showed that cGAS expression was induced in fibrotic liver and kidney, but suppressed in endothelial cells. cGAS genetic deletion promoted liver and kidney fibrosis and pathological angiogenesis, including Meanwhile, cGAS deletion upregulated profibrotic Yes-associated protein (YAP) signaling in endothelial GPCR)-based antagonist that blocks the profibrotic activity of endothelial YAP, attenuated liver and kidney

September 2022 Opposite Effects of Src Family Kinases on YAP and ERK Activation in Pancreatic Cancer combination of insulin and the GPCR agonist neurotensin induced rapid activation of Src family of tyrosine kinases dasatinib, saracatinib, the preferential YES1 inhibitor CH6953755, short interfering RNA (siRNA)-mediated knockdown Surprisingly, our results also demonstrate that exposure to SFK inhibitors, including dasatinib or knockdown of YES and Src induces ERK over-activation in PDAC cells.

Extracellular signal-regulated kinases (ERK), a subset of the mitogen-activated protein kinase (MAPK) Initially, the activation of small GTPases like RAS leads to the activation of the MAP kinase kinase kinases (MAPKKKs), such as RAF. RAF then phosphorylates and activates the MAP kinase kinases (MAPKKs), MEK1 and MEK2, which in turn phosphorylate K., Karnik, S. S., Hunyady, L., Luttrell, L. M., & Lefkowitz, R. J. (2003).

Bongers B J , Gorostiola González M , Wang X , van Vlijmen HWT , Jespers W , Gutiérrez-de-Terán H , Ye K , IJzerman AP , Heitman LH , van Westen GJP.

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pathway caused by BRS3 activation could induce the dephosphorylation and nucleus localization of the Yes-associated protein (YAP), and its association with cell migration was further confirmed by kinase inhibition. Authors Miao Guo , Yan Zhang , Lehao Wu , Ye Sheng , Jiaqi Zhao , Zeyuan Wang , Huiyu Wang , Lu Zhang