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http://purl.uniprot.org/citations/18551195http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18551195http://www.w3.org/2000/01/rdf-schema#comment"cGMP-dependent protein kinase II (cGKII; encoded by PRKG2) is a serine/threonine kinase that is critical for skeletal growth in mammals; in mice, cGKII deficiency results in dwarfism. Using radiographic analysis, we determined that this growth defect was a consequence of an elongated growth plate and impaired chondrocyte hypertrophy. To investigate the mechanism of cGKII-mediated chondrocyte hypertrophy, we performed a kinase substrate array and identified glycogen synthase kinase-3beta (GSK-3beta; encoded by Gsk3b) as a principal phosphorylation target of cGKII. In cultured mouse chondrocytes, phosphorylation-mediated inhibition of GSK-3beta was associated with enhanced hypertrophic differentiation. Furthermore, cGKII induction of chondrocyte hypertrophy was suppressed by cotransfection with a phosphorylation-deficient mutant of GSK-3beta. Analyses of mice with compound deficiencies in both protein kinases (Prkg2(-/-)Gsk3b(+/-)) demonstrated that the growth retardation and elongated growth plate associated with cGKII deficiency were partially rescued by haploinsufficiency of Gsk3b. We found that beta-catenin levels decreased in Prkg2(-/-) mice, while overexpression of cGKII increased the accumulation and transactivation function of beta-catenin in mouse chondroprogenitor ATDC5 cells. This effect was blocked by coexpression of phosphorylation-deficient GSK-3beta. These data indicate that hypertrophic differentiation of growth plate chondrocytes during skeletal growth is promoted by phosphorylation and inactivation of GSK-3beta by cGKII."xsd:string
http://purl.uniprot.org/citations/18551195http://purl.org/dc/terms/identifier"doi:10.1172/jci35243"xsd:string
http://purl.uniprot.org/citations/18551195http://purl.uniprot.org/core/author"Kawaguchi H."xsd:string
http://purl.uniprot.org/citations/18551195http://purl.uniprot.org/core/author"Ikeda T."xsd:string
http://purl.uniprot.org/citations/18551195http://purl.uniprot.org/core/author"Nakamura K."xsd:string
http://purl.uniprot.org/citations/18551195http://purl.uniprot.org/core/author"Shinoda Y."xsd:string
http://purl.uniprot.org/citations/18551195http://purl.uniprot.org/core/author"Saito T."xsd:string
http://purl.uniprot.org/citations/18551195http://purl.uniprot.org/core/author"Ogata N."xsd:string
http://purl.uniprot.org/citations/18551195http://purl.uniprot.org/core/author"Ogasawara T."xsd:string
http://purl.uniprot.org/citations/18551195http://purl.uniprot.org/core/author"Woodgett J.R."xsd:string
http://purl.uniprot.org/citations/18551195http://purl.uniprot.org/core/author"Hofmann F."xsd:string
http://purl.uniprot.org/citations/18551195http://purl.uniprot.org/core/author"Kawasaki Y."xsd:string
http://purl.uniprot.org/citations/18551195http://purl.uniprot.org/core/author"Kawamura N."xsd:string
http://purl.uniprot.org/citations/18551195http://purl.uniprot.org/core/author"Hoshi K."xsd:string
http://purl.uniprot.org/citations/18551195http://purl.uniprot.org/core/author"Chung U.I."xsd:string
http://purl.uniprot.org/citations/18551195http://purl.uniprot.org/core/author"Kamekura S."xsd:string
http://purl.uniprot.org/citations/18551195http://purl.uniprot.org/core/author"Chikuda H."xsd:string
http://purl.uniprot.org/citations/18551195http://purl.uniprot.org/core/author"Kugimiya F."xsd:string
http://purl.uniprot.org/citations/18551195http://purl.uniprot.org/core/author"Yano F."xsd:string
http://purl.uniprot.org/citations/18551195http://purl.uniprot.org/core/author"Higashikawa A."xsd:string
http://purl.uniprot.org/citations/18551195http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18551195http://purl.uniprot.org/core/name"J Clin Invest"xsd:string
http://purl.uniprot.org/citations/18551195http://purl.uniprot.org/core/pages"2506-2515"xsd:string
http://purl.uniprot.org/citations/18551195http://purl.uniprot.org/core/title"Phosphorylation of GSK-3beta by cGMP-dependent protein kinase II promotes hypertrophic differentiation of murine chondrocytes."xsd:string