FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2045755077> ?p ?o ?g. }

• W2045755077 endingPage "4180" @default.
• W2045755077 startingPage "4169" @default.
• W2045755077 abstract "One of the causes of breast cancer is overexpression of the human epidermal growth factor receptor 2 (HER2). Enhanced receptor autophosphorylation and resistance to activation-induced downregulation have been suggested as mechanisms for HER2-induced sustained signaling and cell transformation. However, the molecular mechanisms underlying these possibilities remain incompletely understood. In the current report, we present evidence that show that HER2 overexpression does not lead to receptor hyper-autophosphorylation, but alters patterns in a manner that favors receptor stability and sustained signaling. Specifically, HER2 overexpression blocks epidermal growth factor receptor (EGFR) tyrosine phosphorylation on Y1045 and Y1068, the known docking sites of c-Cbl and Grb2, respectively, whereas promoting phosphorylation on Y1173, the known docking site of the Gab adaptor proteins and phospholipase C gamma. Under these conditions, HER2 itself is phosphorylated on Y1221/1222, with no known role, and on Y1248 that corresponds to Y1173 of EGFR. Interestingly, suppressed EGFR autophosphorylation on the Grb2 and c-Cbl-binding sites correlated with receptor stability and sustained signaling, suggesting that HER2 accomplishes these tasks by altering autophosphorylation patterns. In conformity with these findings, mutation of the Grb2-binding site on EGFR (Y1068F-EGFR) conferred resistance to ligand-induced degradation, which in turn induced sustained signaling, and increased cell proliferation and transformation. These findings suggest that the Grb2-binding site on EGFR is redundant for signaling, but critical for receptor regulation. On the other hand, mutation of the putative Grb2-binding site in HER2 (Y1139) did not affect stability, signaling or transformation, suggesting that Y1139 in HER2 may not serve as a Grb2-binding site. In agreement with the role of EGFR in HER2 signaling, inhibition of EGFR expression reduced HER2-induced anchorage-independent growth and tumorigenesis. These results imply that complementing HER2-targeted therapies with anti-EGFR drugs may be beneficial in HER2-positive breast cancer." @default.
• W2045755077 created "2016-06-24" @default.
• W2045755077 creator A5023825859 @default.
• W2045755077 creator A5027863997 @default.
• W2045755077 creator A5088820265 @default.
• W2045755077 date "2012-10-01" @default.
• W2045755077 modified "2023-10-16" @default.
• W2045755077 title "HER2 stabilizes EGFR and itself by altering autophosphorylation patterns in a manner that overcomes regulatory mechanisms and promotes proliferative and transformation signaling" @default.
• W2045755077 cites W1489118721 @default.
• W2045755077 cites W1574457161 @default.
• W2045755077 cites W1938129101 @default.
• W2045755077 cites W1957044910 @default.
• W2045755077 cites W1963913479 @default.
• W2045755077 cites W1966658428 @default.
• W2045755077 cites W1972322040 @default.
• W2045755077 cites W1973415230 @default.
• W2045755077 cites W1973681162 @default.
• W2045755077 cites W1978635892 @default.
• W2045755077 cites W1980039397 @default.
• W2045755077 cites W1984238642 @default.
• W2045755077 cites W1987896973 @default.
• W2045755077 cites W1988127794 @default.
• W2045755077 cites W1989783897 @default.
• W2045755077 cites W1992864103 @default.
• W2045755077 cites W1995085157 @default.
• W2045755077 cites W1995337883 @default.
• W2045755077 cites W2005337889 @default.
• W2045755077 cites W2006501717 @default.
• W2045755077 cites W2007256480 @default.
• W2045755077 cites W2012233176 @default.
• W2045755077 cites W2019772485 @default.
• W2045755077 cites W2032422012 @default.
• W2045755077 cites W2037266556 @default.
• W2045755077 cites W2041030848 @default.
• W2045755077 cites W2053799953 @default.
• W2045755077 cites W2056086335 @default.
• W2045755077 cites W2058620780 @default.
• W2045755077 cites W2061224647 @default.
• W2045755077 cites W2064282349 @default.
• W2045755077 cites W2074877259 @default.
• W2045755077 cites W2077483055 @default.
• W2045755077 cites W2078747821 @default.
• W2045755077 cites W2082852872 @default.
• W2045755077 cites W2083053655 @default.
• W2045755077 cites W2092897704 @default.
• W2045755077 cites W2094630875 @default.
• W2045755077 cites W2100281377 @default.
• W2045755077 cites W2100794900 @default.
• W2045755077 cites W2103484524 @default.
• W2045755077 cites W2111004422 @default.
• W2045755077 cites W2117377079 @default.
• W2045755077 cites W2121043575 @default.
• W2045755077 cites W2125251546 @default.
• W2045755077 cites W2125947965 @default.
• W2045755077 cites W2129936304 @default.
• W2045755077 cites W2135117965 @default.
• W2045755077 cites W2139444209 @default.
• W2045755077 cites W2141452917 @default.
• W2045755077 cites W2143600397 @default.
• W2045755077 cites W2145734670 @default.
• W2045755077 doi "https://doi.org/10.1038/onc.2012.418" @default.
• W2045755077 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3538112" @default.
• W2045755077 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23027125" @default.
• W2045755077 hasPublicationYear "2012" @default.
• W2045755077 type Work @default.
• W2045755077 sameAs 2045755077 @default.
• W2045755077 citedByCount "53" @default.
• W2045755077 countsByYear W20457550772013 @default.
• W2045755077 countsByYear W20457550772014 @default.
• W2045755077 countsByYear W20457550772015 @default.
• W2045755077 countsByYear W20457550772016 @default.
• W2045755077 countsByYear W20457550772017 @default.
• W2045755077 countsByYear W20457550772018 @default.
• W2045755077 countsByYear W20457550772019 @default.
• W2045755077 countsByYear W20457550772020 @default.
• W2045755077 countsByYear W20457550772021 @default.
• W2045755077 countsByYear W20457550772022 @default.
• W2045755077 countsByYear W20457550772023 @default.
• W2045755077 crossrefType "journal-article" @default.
• W2045755077 hasAuthorship W2045755077A5023825859 @default.
• W2045755077 hasAuthorship W2045755077A5027863997 @default.
• W2045755077 hasAuthorship W2045755077A5088820265 @default.
• W2045755077 hasBestOaLocation W20457550771 @default.
• W2045755077 hasConcept C101544691 @default.
• W2045755077 hasConcept C115456853 @default.
• W2045755077 hasConcept C11960822 @default.
• W2045755077 hasConcept C150109051 @default.
• W2045755077 hasConcept C170493617 @default.
• W2045755077 hasConcept C177917778 @default.
• W2045755077 hasConcept C183786373 @default.
• W2045755077 hasConcept C26375932 @default.
• W2045755077 hasConcept C2776362946 @default.
• W2045755077 hasConcept C2779438470 @default.
• W2045755077 hasConcept C502942594 @default.
• W2045755077 hasConcept C55493867 @default.
• W2045755077 hasConcept C62478195 @default.
• W2045755077 hasConcept C86803240 @default.
• W2045755077 hasConcept C95444343 @default.

• next