| http://purl.uniprot.org/citations/11579100 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/11579100 | http://www.w3.org/2000/01/rdf-schema#comment | "Signal transducers and activators of transcription (STATs) comprise a family of cytoplasmic signaling proteins that participates in normal cellular responses to cytokines and growth factors. Frequently, however, constitutive activation of certain STAT family members, particularly Stat3, has accompanied a wide variety of human malignancies. To identify small molecule inhibitors of Stat3, we investigated the ability of the Stat3 SH2 domain-binding peptide, PY*LKTK (where Y* represents phosphotyrosine), to disrupt Stat3 activity in vitro. The presence of PY*LKTK, but not PYLKTK or PFLKTK, in nuclear extracts results in significant reduction in the levels of DNA binding activities of Stat3, to a lesser extent of Stat1, and with no effect on that of Stat5. Analyses of alanine scanning mutagenesis and deletion derivatives of PY*LKTK reveal that the Leu residue at the Y+1 position and a substituent at the Y-1 position (but not necessarily Pro) are essential for the disruption of active Stat3, thereby mapping the minimum active sequence to the tripeptide, XY*L. Studies involving bead-coupled PY*LKTK peptide demonstrate that this phosphopeptide directly complexes with Stat3 monomers in vitro, suggesting that PY*LKTK disrupts Stat3:Stat3 dimers. As evidence for the functional importance of peptide-directed inhibition of Stat3, PY*LKTK-mts (mts, membrane translocating sequence) selectively inhibits constitutive and ligand-induced Stat3 activation in vivo. Furthermore, PY*LKTK-mts suppresses transformation by the Src oncoprotein, which has been shown previously to require constitutive Stat3 activation. Altogether, we have identified a minimal peptide that inhibits Stat3 signaling and provides the conceptual basis for use of this peptide as a lead for novel peptidomimetic drug design."xsd:string |
| http://purl.uniprot.org/citations/11579100 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m107527200"xsd:string |
| http://purl.uniprot.org/citations/11579100 | http://purl.uniprot.org/core/author | "Chen Z."xsd:string |
| http://purl.uniprot.org/citations/11579100 | http://purl.uniprot.org/core/author | "Kim J.S."xsd:string |
| http://purl.uniprot.org/citations/11579100 | http://purl.uniprot.org/core/author | "Zhang Y."xsd:string |
| http://purl.uniprot.org/citations/11579100 | http://purl.uniprot.org/core/author | "Ryan D."xsd:string |
| http://purl.uniprot.org/citations/11579100 | http://purl.uniprot.org/core/author | "Laudano A."xsd:string |
| http://purl.uniprot.org/citations/11579100 | http://purl.uniprot.org/core/author | "Hamilton A.D."xsd:string |
| http://purl.uniprot.org/citations/11579100 | http://purl.uniprot.org/core/author | "Jove R."xsd:string |
| http://purl.uniprot.org/citations/11579100 | http://purl.uniprot.org/core/author | "Turkson J."xsd:string |
| http://purl.uniprot.org/citations/11579100 | http://purl.uniprot.org/core/author | "Haura E."xsd:string |
| http://purl.uniprot.org/citations/11579100 | http://purl.uniprot.org/core/author | "Sebti S."xsd:string |
| http://purl.uniprot.org/citations/11579100 | http://purl.uniprot.org/core/date | "2001"xsd:gYear |
| http://purl.uniprot.org/citations/11579100 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/11579100 | http://purl.uniprot.org/core/pages | "45443-45455"xsd:string |
| http://purl.uniprot.org/citations/11579100 | http://purl.uniprot.org/core/title | "Phosphotyrosyl peptides block Stat3-mediated DNA binding activity, gene regulation, and cell transformation."xsd:string |
| http://purl.uniprot.org/citations/11579100 | http://purl.uniprot.org/core/volume | "276"xsd:string |
| http://purl.uniprot.org/citations/11579100 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/11579100 |
| http://purl.uniprot.org/citations/11579100 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/11579100 |
| http://purl.uniprot.org/uniprot/P42227#attribution-3F5E34C3D208528B8E1490542B124658 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/11579100 |
| http://purl.uniprot.org/uniprot/P42227#attribution-C24A15AA9C5F0D7024B03CEB691C1EE2 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/11579100 |
| http://purl.uniprot.org/uniprot/#_A0A087WSP5-mappedCitation-11579100 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/11579100 |
| http://purl.uniprot.org/uniprot/#_A0A087WSQ5-mappedCitation-11579100 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/11579100 |
| http://purl.uniprot.org/uniprot/#_A0A087WRI1-mappedCitation-11579100 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/11579100 |