FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2329506938> ?p ?o ?g. }

• W2329506938 abstract "MLK3 is a member of MLK sub-family that belongs to the family of MAP kinase kinase kinase (MAP3K). The MLK family members are characterized by the presence of signature sequences of Ser/Thr and Tyr kinases within their catalytic domain. The detailed physiological function of MLK3 is yet to be deciphered fully, however the available data suggest that in neuronal cells, MLK3 plays role of a pro-apoptotic kinase. The function of MLK3 in any type of cancer is not known. Interestingly the C-terminal tail of MLK3 contains consensus sequences for various protein-protein interactions and phosphorylation sites for numerous kinases. The C-terminal tail also contains Ser/Thr-Pro sequence, a consensus sequence for prolyl isomerase (Pin1), which has been reported to be over-expressed in cancer cells, including in breast cancer cells and primary tumors. Our initial hypothesis was that probably Pin1 binds to MLK3 and regulates MLK39s kinase activity. Our in vivo binding indeed suggested that Pin1 binds to MLK3 via PPI domain robustly and to certain extent through WW domain. The binding of Pin1 did not alter the kinase activity of MLK3. Interestingly, counterintuitive to our initial hypothesis, we observed that MLK3 was able to phosphorylate Pin1 and alter Pin19s isomerase activity. We also identified S138 as a phosphorylation site on Pin1 and raised p-S138 antibody. Since, Pin1 is known to drive G2-M-cell cycle transition, we examined whether phosphorylation of Pin1 promotes cell cycle progression. Our data indicated that phospho-S138 Pin1 increased the G2-M transition of cell cycle. Pin1 is reported to be a nuclear protein; however it is not known whether this translocation of Pin1is regulated by any protein. We observed that Pin1 was translocated to nucleus upon phosphorylation by MLK3 at S138 site and the phospho-S138 Pin1 was highly expressed in breast cancer cell lines and tumors, compared to non-transformed breast epithelial cell line and normal breast tissues respectively. The breast cancer tissue arrays analyzed also showed that phospho-S138 was highly expressed in tumors compared to normal breast tissue and the intensity of staining was significantly higher in tumors as well. Taken together, our data suggest that phosphorylation of Pin1 by MLK3 drives G2-M transition and promote breast cancer pathogenesis. Thus targeting MLK3 or Pin1 may prove beneficial to control breast cancer tumorigenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5065." @default.
• W2329506938 created "2016-06-24" @default.
• W2329506938 creator A5028563213 @default.
• W2329506938 creator A5044411309 @default.
• W2329506938 creator A5046360981 @default.
• W2329506938 creator A5061500801 @default.
• W2329506938 creator A5081839578 @default.
• W2329506938 date "2010-04-15" @default.
• W2329506938 modified "2023-09-27" @default.
• W2329506938 title "Abstract 5065: Phosphorylation of Peptidyl prolyl isomerase 1 by Mixed Lineage Kinase 3 promotes breast cancer pathogenesis" @default.
• W2329506938 doi "https://doi.org/10.1158/1538-7445.am10-5065" @default.
• W2329506938 hasPublicationYear "2010" @default.
• W2329506938 type Work @default.
• W2329506938 sameAs 2329506938 @default.
• W2329506938 citedByCount "0" @default.
• W2329506938 crossrefType "proceedings-article" @default.
• W2329506938 hasAuthorship W2329506938A5028563213 @default.
• W2329506938 hasAuthorship W2329506938A5044411309 @default.
• W2329506938 hasAuthorship W2329506938A5046360981 @default.
• W2329506938 hasAuthorship W2329506938A5061500801 @default.
• W2329506938 hasAuthorship W2329506938A5081839578 @default.
• W2329506938 hasConcept C104317684 @default.
• W2329506938 hasConcept C11960822 @default.
• W2329506938 hasConcept C124160383 @default.
• W2329506938 hasConcept C137361374 @default.
• W2329506938 hasConcept C143065580 @default.
• W2329506938 hasConcept C154472170 @default.
• W2329506938 hasConcept C181199279 @default.
• W2329506938 hasConcept C184235292 @default.
• W2329506938 hasConcept C2781098309 @default.
• W2329506938 hasConcept C2781264208 @default.
• W2329506938 hasConcept C2910677434 @default.
• W2329506938 hasConcept C32619005 @default.
• W2329506938 hasConcept C502942594 @default.
• W2329506938 hasConcept C51853150 @default.
• W2329506938 hasConcept C55493867 @default.
• W2329506938 hasConcept C82495950 @default.
• W2329506938 hasConcept C86803240 @default.
• W2329506938 hasConcept C95444343 @default.
• W2329506938 hasConcept C97029542 @default.
• W2329506938 hasConceptScore W2329506938C104317684 @default.
• W2329506938 hasConceptScore W2329506938C11960822 @default.
• W2329506938 hasConceptScore W2329506938C124160383 @default.
• W2329506938 hasConceptScore W2329506938C137361374 @default.
• W2329506938 hasConceptScore W2329506938C143065580 @default.
• W2329506938 hasConceptScore W2329506938C154472170 @default.
• W2329506938 hasConceptScore W2329506938C181199279 @default.
• W2329506938 hasConceptScore W2329506938C184235292 @default.
• W2329506938 hasConceptScore W2329506938C2781098309 @default.
• W2329506938 hasConceptScore W2329506938C2781264208 @default.
• W2329506938 hasConceptScore W2329506938C2910677434 @default.
• W2329506938 hasConceptScore W2329506938C32619005 @default.
• W2329506938 hasConceptScore W2329506938C502942594 @default.
• W2329506938 hasConceptScore W2329506938C51853150 @default.
• W2329506938 hasConceptScore W2329506938C55493867 @default.
• W2329506938 hasConceptScore W2329506938C82495950 @default.
• W2329506938 hasConceptScore W2329506938C86803240 @default.
• W2329506938 hasConceptScore W2329506938C95444343 @default.
• W2329506938 hasConceptScore W2329506938C97029542 @default.
• W2329506938 hasLocation W23295069381 @default.
• W2329506938 hasOpenAccess W2329506938 @default.
• W2329506938 hasPrimaryLocation W23295069381 @default.
• W2329506938 hasRelatedWork W1979238734 @default.
• W2329506938 hasRelatedWork W1983745682 @default.
• W2329506938 hasRelatedWork W2001141506 @default.
• W2329506938 hasRelatedWork W2007112356 @default.
• W2329506938 hasRelatedWork W2049369808 @default.
• W2329506938 hasRelatedWork W2071062085 @default.
• W2329506938 hasRelatedWork W2209218388 @default.
• W2329506938 hasRelatedWork W2317833009 @default.
• W2329506938 hasRelatedWork W2324543666 @default.
• W2329506938 hasRelatedWork W2329944909 @default.
• W2329506938 hasRelatedWork W2395155128 @default.
• W2329506938 hasRelatedWork W2523880877 @default.
• W2329506938 hasRelatedWork W2561634652 @default.
• W2329506938 hasRelatedWork W2564229059 @default.
• W2329506938 hasRelatedWork W2748559592 @default.
• W2329506938 hasRelatedWork W2760989328 @default.
• W2329506938 hasRelatedWork W2774445945 @default.
• W2329506938 hasRelatedWork W3082482621 @default.
• W2329506938 hasRelatedWork W3113395112 @default.
• W2329506938 hasRelatedWork W3114619452 @default.
• W2329506938 isParatext "false" @default.
• W2329506938 isRetracted "false" @default.
• W2329506938 magId "2329506938" @default.
• W2329506938 workType "article" @default.