PMC:4307189 / 40627-42151
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4307189","sourcedb":"PMC","sourceid":"4307189","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4307189","text":"Cross-talk between EGFR/ErbB and GPCR signaling\nBetween EGFR/ErbB and GPCR signaling pathways, we found KIT:GNAQ (in Reactome), MDM2:GNAQ (in Reactome and WikiPathway), CBL:GNAQ (in Reactome), FGFR2:GNAQ (in Reactome), PDGFRA:GNAQ (in Reactome), KIT:TSHR (in Reactome), MDM2:TSHR (in Reactome), CBL:TSHR (in Reactome), PDGFRA:TSHR (in Reactome), KIT:GNAS (in Reactome), MDM2:GNAS (in Reactome and WikiPathway), KIT:SMO (in Reactome), MDM2:SMO (in Reactome), TP53:GNAQ (in WikiPathway), and MYC:GNAQ (in WikiPathway). GPCR-like signaling contributes to acquired drug resistance after being mediated by Smoothened (SMO) via activating Gli, a canonical hedgehog (Hh) transcription factor [57]. GPCR and EGFR/ErbB over-expression often contributes to cancer growth. Cross-talk between the two at the receptor level contributes to HNSCC (head and neck squamous cell carcinoma) via triggering EGFR/ErbB signaling by a GPCR ligand [58]. For the MDM2:SMO cross-talk, found between the EGFR/ErbB and GPCR signaling pathways, a SMO-mutant from Hh signal transducer activates PI3K/Akt/Gli pathway that eventually increases MDM2 phosphorylation [59]. This in turn increases MDM2-mediated p53 degradation and thus reduces p53-induced apoptosis [59]. Furthermore, recently it has been reported that SMO (Hh signal transducer) functions like a G-protein coupled receptor due to its structural resemblance to GPCRs [60,61] which may be further evidence for a drug-resistant cross-talk between hedgehog signaling and EGFR/ErbB signaling [1].","divisions":[{"label":"title","span":{"begin":0,"end":47}}],"tracks":[{"project":"2_test","denotations":[{"id":"25599599-24393163-14868158","span":{"begin":686,"end":688},"obj":"24393163"},{"id":"25599599-18359851-14868159","span":{"begin":1134,"end":1136},"obj":"18359851"},{"id":"25599599-18359851-14868160","span":{"begin":1232,"end":1234},"obj":"18359851"},{"id":"25599599-20207148-14868161","span":{"begin":1400,"end":1402},"obj":"20207148"},{"id":"25599599-19211052-14868162","span":{"begin":1403,"end":1405},"obj":"19211052"},{"id":"25599599-23542173-14868163","span":{"begin":1521,"end":1522},"obj":"23542173"}],"attributes":[{"subj":"25599599-24393163-14868158","pred":"source","obj":"2_test"},{"subj":"25599599-18359851-14868159","pred":"source","obj":"2_test"},{"subj":"25599599-18359851-14868160","pred":"source","obj":"2_test"},{"subj":"25599599-20207148-14868161","pred":"source","obj":"2_test"},{"subj":"25599599-19211052-14868162","pred":"source","obj":"2_test"},{"subj":"25599599-23542173-14868163","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#93bbec","default":true}]}]}}