| http://purl.uniprot.org/citations/10022928 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/10022928 | http://www.w3.org/2000/01/rdf-schema#comment | "Shp-2 is an SH2 domain-containing protein tyrosine phosphatase. Although the mechanism remains to be defined, substantial experimental data suggest that Shp-2 is primarily a positive regulator in cell growth and development. We present evidence here that Shp-2, while acting to promote mitogenic signals, also functions as a negative effector in interferon (IFN)-induced growth-inhibitory and apoptotic pathways. Treatment of mouse fibroblast cells lacking a functional Shp-2 with IFN-alpha or IFN-gamma resulted in an augmented suppression of cell viability compared to that of wild-type cells. To dissect the molecular mechanism, we examined IFN-induced activation of signal transducers and activators of transcription (STATs) by electrophoretic mobility shift assay, using a specific DNA probe (hSIE). The amounts of STAT proteins bound to hSIE upon IFN-alpha or IFN-gamma stimulation were significantly increased in Shp-2(-/-) cells. Consistently, tyrosine phosphorylation levels of Stat1 upon IFN-gamma treatment and, to a lesser extent, upon IFN-alpha stimulation were markedly elevated in mutant cells. Furthermore, IFN-gamma induced a higher level of caspase 1 expression in Shp-2(-/-) cells than in wild-type cells. Reintroduction of wild-type Shp-2 protein reversed the hypersensitivity of Shp-2(-/-) fibroblasts to the cytotoxic effect of IFN-alpha and IFN-gamma. Excessive activation of STATs by IFNs was also diminished in mutant cells in which Shp-2 had been reintroduced. Together, these results establish that Shp-2 functions as a negative regulator of the Jak/STAT pathway. We propose that Shp-2 acts to promote cell growth and survival through two mechanisms, i.e., the stimulation of growth factor-initiated mitogenic pathways and the suppression of cytotoxic effect elicited by cytokines, such as IFNs."xsd:string |
| http://purl.uniprot.org/citations/10022928 | http://purl.org/dc/terms/identifier | "doi:10.1128/mcb.19.3.2416"xsd:string |
| http://purl.uniprot.org/citations/10022928 | http://purl.uniprot.org/core/author | "You M."xsd:string |
| http://purl.uniprot.org/citations/10022928 | http://purl.uniprot.org/core/author | "Yu D.H."xsd:string |
| http://purl.uniprot.org/citations/10022928 | http://purl.uniprot.org/core/author | "Feng G.S."xsd:string |
| http://purl.uniprot.org/citations/10022928 | http://purl.uniprot.org/core/date | "1999"xsd:gYear |
| http://purl.uniprot.org/citations/10022928 | http://purl.uniprot.org/core/name | "Mol Cell Biol"xsd:string |
| http://purl.uniprot.org/citations/10022928 | http://purl.uniprot.org/core/pages | "2416-2424"xsd:string |
| http://purl.uniprot.org/citations/10022928 | http://purl.uniprot.org/core/title | "Shp-2 tyrosine phosphatase functions as a negative regulator of the interferon-stimulated Jak/STAT pathway."xsd:string |
| http://purl.uniprot.org/citations/10022928 | http://purl.uniprot.org/core/volume | "19"xsd:string |
| http://purl.uniprot.org/citations/10022928 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/10022928 |
| http://purl.uniprot.org/citations/10022928 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/10022928 |
| http://purl.uniprot.org/uniprot/#_P52630-mappedCitation-10022928 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10022928 |
| http://purl.uniprot.org/uniprot/#_P42224-mappedCitation-10022928 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10022928 |
| http://purl.uniprot.org/uniprot/#_P01562-mappedCitation-10022928 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10022928 |
| http://purl.uniprot.org/uniprot/#_P01563-mappedCitation-10022928 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10022928 |
| http://purl.uniprot.org/uniprot/#_P01566-mappedCitation-10022928 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10022928 |
| http://purl.uniprot.org/uniprot/#_P01567-mappedCitation-10022928 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10022928 |
| http://purl.uniprot.org/uniprot/#_P01568-mappedCitation-10022928 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10022928 |
| http://purl.uniprot.org/uniprot/#_P01569-mappedCitation-10022928 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10022928 |
| http://purl.uniprot.org/uniprot/#_P01570-mappedCitation-10022928 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10022928 |
| http://purl.uniprot.org/uniprot/#_P01571-mappedCitation-10022928 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10022928 |
| http://purl.uniprot.org/uniprot/#_P01574-mappedCitation-10022928 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10022928 |
| http://purl.uniprot.org/uniprot/#_P17181-mappedCitation-10022928 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10022928 |