title: Regulation of the Hippo-YAP pathway by protease-activated receptors (PARs).
abstract: The Hippo signaling pathway plays a crucial role in tissue growth and tumorigenesis. Core components of the Hippo pathway include the MST1/2 and Lats1/2 kinases. Acting downstream from the Hippo pathway are the YAP/TAZ transcription coactivators, which are inhibited through phosphorylation by Lats. However, upstream signals that regulate the Hippo pathway have not been well delineated. Here we report that stimulation of protease-activated receptors (PARs) activates YAP/TAZ by decreasing phosphorylation and increasing nuclear localization. PAR1 acts through G(12/13) and Rho GTPase to inhibit the Lats1/2 kinase. Our observations establish thrombin as a physiological signal for the Hippo pathway and implicate Hippo-YAP as a key downstream signaling branch of PAR activation.
authors.affiliation: Department of Pharmacology, Moores Cancer Center, University of California at San Diego, La Jolla, California 92093, USA.
authors.forename: Jung-Soon
authors.initials: JS
authors.lastname: Mo
authors.forename: Fa-Xing
authors.initials: FX
authors.lastname: Yu
authors.forename: Rui
authors.initials: R
authors.lastname: Gong
authors.forename: Joan Heller
authors.initials: JH
authors.lastname: Brown
authors.forename: Kun-Liang
authors.initials: KL
authors.lastname: Guan
mesh_terms: D008841:Actin Cytoskeleton; D000217:Acyltransferases; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000201:enzymology; D004789:Enzyme Activation / Q000502:physiology; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000378:metabolism; D044462:Receptors, Proteinase-Activated / Q000819:agonists / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D009842:Oligopeptides; D034741:RNA, Small Interfering; D044462:Receptors, Proteinase-Activated; C504808:Ser-Phe-Phe-Leu-Arg-Asn; D014157:Transcription Factors; C456659:YY1AP1 protein, human; D000217:Acyltransferases; C108675:TAFAZZIN protein, human; D017346:Protein Serine-Threonine Kinases