| http://purl.uniprot.org/citations/12388746 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/12388746 | http://www.w3.org/2000/01/rdf-schema#comment | "It is well established that mammary gland development and lactation are tightly controlled by prolactin signaling. Binding of prolactin to its cognate receptor (Prl-R) leads to activation of the Jak-2 tyrosine kinase and the recruitment/tyrosine phosphorylation of STAT5a. However, the mechanisms for attenuating the Prl-R/Jak-2/STAT5a signaling cascade are just now being elucidated. Here, we present evidence that caveolin-1 functions as a novel suppressor of cytokine signaling in the mammary gland, akin to the SOCS family of proteins. Specifically, we show that caveolin-1 expression blocks prolactin-induced activation of a STAT5a-responsive luciferase reporter in mammary epithelial cells. Furthermore, caveolin-1 expression inhibited prolactin-induced STAT5a tyrosine phosphorylation and DNA binding activity, suggesting that caveolin-1 may negatively regulate the Jak-2 tyrosine kinase. Because the caveolin-scaffolding domain bears a striking resemblance to the SOCS pseudosubstrate domain, we examined whether Jak-2 associates with caveolin-1. In accordance with this homology, we demonstrate that Jak-2 cofractionates and coimmunoprecipitates with caveolin-1. We next tested the in vivo relevance of these findings using female Cav-1 (-/-) null mice. If caveolin-1 normally functions as a suppressor of cytokine signaling in the mammary gland, then Cav-1 null mice should show premature development of the lobuloalveolar compartment because of hyperactivation of the prolactin signaling cascade via disinhibition of Jak-2. In accordance with this prediction, Cav-1 null mice show accelerated development of the lobuloalveolar compartment, premature milk production, and hyperphosphorylation of STAT5a (pY694) at its Jak-2 phosphorylation site. In addition, the Ras-p42/44 MAPK cascade is hyper-activated. Because a similar premature lactation phenotype is observed in SOCS1 (-/-) null mice, we conclude that caveolin-1 is a novel suppressor of cytokine signaling."xsd:string |
| http://purl.uniprot.org/citations/12388746 | http://purl.org/dc/terms/identifier | "doi:10.1091/mbc.02-05-0071"xsd:string |
| http://purl.uniprot.org/citations/12388746 | http://purl.uniprot.org/core/author | "Lee H."xsd:string |
| http://purl.uniprot.org/citations/12388746 | http://purl.uniprot.org/core/author | "Razani B."xsd:string |
| http://purl.uniprot.org/citations/12388746 | http://purl.uniprot.org/core/author | "Lisanti M.P."xsd:string |
| http://purl.uniprot.org/citations/12388746 | http://purl.uniprot.org/core/author | "Russell R.G."xsd:string |
| http://purl.uniprot.org/citations/12388746 | http://purl.uniprot.org/core/author | "Park D.S."xsd:string |
| http://purl.uniprot.org/citations/12388746 | http://purl.uniprot.org/core/author | "Parlow A.F."xsd:string |
| http://purl.uniprot.org/citations/12388746 | http://purl.uniprot.org/core/author | "Pestell R.G."xsd:string |
| http://purl.uniprot.org/citations/12388746 | http://purl.uniprot.org/core/author | "Nguyen A.V."xsd:string |
| http://purl.uniprot.org/citations/12388746 | http://purl.uniprot.org/core/author | "Frank P.G."xsd:string |
| http://purl.uniprot.org/citations/12388746 | http://purl.uniprot.org/core/author | "Hulit J."xsd:string |
| http://purl.uniprot.org/citations/12388746 | http://purl.uniprot.org/core/date | "2002"xsd:gYear |
| http://purl.uniprot.org/citations/12388746 | http://purl.uniprot.org/core/name | "Mol Biol Cell"xsd:string |
| http://purl.uniprot.org/citations/12388746 | http://purl.uniprot.org/core/pages | "3416-3430"xsd:string |
| http://purl.uniprot.org/citations/12388746 | http://purl.uniprot.org/core/title | "Caveolin-1-deficient mice show accelerated mammary gland development during pregnancy, premature lactation, and hyperactivation of the Jak-2/STAT5a signaling cascade."xsd:string |
| http://purl.uniprot.org/citations/12388746 | http://purl.uniprot.org/core/volume | "13"xsd:string |
| http://purl.uniprot.org/citations/12388746 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/12388746 |
| http://purl.uniprot.org/citations/12388746 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/12388746 |
| http://purl.uniprot.org/uniprot/P49817#attribution-A09B5C87EFC75FAE233C36B9FEDBF1B0 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/12388746 |
| http://purl.uniprot.org/uniprot/P49817#attribution-F5B125254EBD3794EABDC0ADCE89A64E | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/12388746 |
| http://purl.uniprot.org/uniprot/P49817#attribution-F9F15F29FED9467A5EB521543E368903 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/12388746 |
| http://purl.uniprot.org/uniprot/Q03135#attribution-F9F15F29FED9467A5EB521543E368903 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/12388746 |
| http://purl.uniprot.org/uniprot/Q62120#attribution-F9F15F29FED9467A5EB521543E368903 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/12388746 |