FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2092235133> ?p ?o ?g. }

• W2092235133 endingPage "e44363" @default.
• W2092235133 startingPage "e44363" @default.
• W2092235133 abstract "Background Epidermal growth factor receptor (EGFR) internalization following ligand binding controls EGFR downstream pathway signaling activity. Internalized EGFR is poly-ubiquitinated by Cbl to promote lysosome-mediated degradation and signal downregulation. ACK1 is a non-receptor tyrosine kinase that interacts with ubiquitinated EGFR to facilitate EGFR degradation. Dynamic reorganization of the cortical actin cytoskeleton controlled by the actin related protein (Arp)2/3 complex is important in regulating EGFR endocytosis and vesicle trafficking. How ACK1-mediated EGFR internalization cooperates with Arp2/3-based actin dynamics during EGFR downregulation is unclear. Methodology/Principal Findings Here we show that ACK1 directly binds and phosphorylates the Arp2/3 regulatory protein cortactin, potentially providing a direct link to Arp2/3-based actin dynamics during EGFR degradation. Co-immunoprecipitation analysis indicates that the cortactin SH3 domain is responsible for binding to ACK1. In vitro kinase assays demonstrate that ACK1 phosphorylates cortactin on key tyrosine residues that create docking sites for adaptor proteins responsible for enhancing Arp2/3 nucleation. Analysis with phosphorylation-specific antibodies determined that EGFR-induced cortactin tyrosine phosphorylation is diminished coincident with EGFR degradation, whereas ERK1/2 cortactin phosphorylation utilized in promoting activation of the Arp2/3 regulator N-WASp is sustained during EGFR downregulation. Cortactin and ACK1 localize to internalized vesicles containing EGF bound to EGFR visualized by confocal microscopy. RNA interference and rescue studies indicate that ACK1 and the cortactin SH3 domain are essential for ligand-mediated EGFR internalization. Conclusions/Significance Cortactin is a direct binding partner and novel substrate of ACK1. Tyrosine phosphorylation of cortactin by ACK1 creates an additional means to amplify Arp2/3 dynamics through N-WASp activation, potentially contributing to the overall necessary tensile and/or propulsive forces utilized during EGFR endocytic internalization and trafficking involved in receptor degradation." @default.
• W2092235133 created "2016-06-24" @default.
• W2092235133 creator A5026139172 @default.
• W2092235133 creator A5044520173 @default.
• W2092235133 date "2012-08-30" @default.
• W2092235133 modified "2023-09-27" @default.
• W2092235133 title "Cortactin Is a Substrate of Activated Cdc42-Associated Kinase 1 (ACK1) during Ligand-induced Epidermal Growth Factor Receptor Downregulation" @default.
• W2092235133 cites W1522989648 @default.
• W2092235133 cites W1532527807 @default.
• W2092235133 cites W1566432282 @default.
• W2092235133 cites W1733018497 @default.
• W2092235133 cites W1794615995 @default.
• W2092235133 cites W1832262637 @default.
• W2092235133 cites W1942708165 @default.
• W2092235133 cites W1967238741 @default.
• W2092235133 cites W1968323673 @default.
• W2092235133 cites W1971692317 @default.
• W2092235133 cites W1975126814 @default.
• W2092235133 cites W1982323979 @default.
• W2092235133 cites W1985169370 @default.
• W2092235133 cites W1986276126 @default.
• W2092235133 cites W1987113772 @default.
• W2092235133 cites W1987769201 @default.
• W2092235133 cites W1992216985 @default.
• W2092235133 cites W1993077125 @default.
• W2092235133 cites W1993314049 @default.
• W2092235133 cites W1994545036 @default.
• W2092235133 cites W1996031315 @default.
• W2092235133 cites W1999816397 @default.
• W2092235133 cites W2000966286 @default.
• W2092235133 cites W2001532503 @default.
• W2092235133 cites W2003603726 @default.
• W2092235133 cites W2010781630 @default.
• W2092235133 cites W2012480312 @default.
• W2092235133 cites W2012915718 @default.
• W2092235133 cites W2013904065 @default.
• W2092235133 cites W2014868351 @default.
• W2092235133 cites W2019772485 @default.
• W2092235133 cites W2029086133 @default.
• W2092235133 cites W2033264288 @default.
• W2092235133 cites W2040010587 @default.
• W2092235133 cites W2049332771 @default.
• W2092235133 cites W2051410189 @default.
• W2092235133 cites W2058741346 @default.
• W2092235133 cites W2061152791 @default.
• W2092235133 cites W2061913305 @default.
• W2092235133 cites W2064492584 @default.
• W2092235133 cites W2068091252 @default.
• W2092235133 cites W2073476855 @default.
• W2092235133 cites W2075090444 @default.
• W2092235133 cites W2075188939 @default.
• W2092235133 cites W2079693341 @default.
• W2092235133 cites W2080483074 @default.
• W2092235133 cites W2081787725 @default.
• W2092235133 cites W2082315732 @default.
• W2092235133 cites W2083140246 @default.
• W2092235133 cites W2088948163 @default.
• W2092235133 cites W2089663915 @default.
• W2092235133 cites W2091322376 @default.
• W2092235133 cites W2092089306 @default.
• W2092235133 cites W2092127177 @default.
• W2092235133 cites W2093390493 @default.
• W2092235133 cites W2097312459 @default.
• W2092235133 cites W2098278940 @default.
• W2092235133 cites W2102197740 @default.
• W2092235133 cites W2107150099 @default.
• W2092235133 cites W2112229259 @default.
• W2092235133 cites W2112915535 @default.
• W2092235133 cites W2113509699 @default.
• W2092235133 cites W2122209825 @default.
• W2092235133 cites W2125251546 @default.
• W2092235133 cites W2125743967 @default.
• W2092235133 cites W2132448632 @default.
• W2092235133 cites W2133244083 @default.
• W2092235133 cites W2133796471 @default.
• W2092235133 cites W2134240326 @default.
• W2092235133 cites W2138815602 @default.
• W2092235133 cites W2139130671 @default.
• W2092235133 cites W2145072524 @default.
• W2092235133 cites W2145273873 @default.
• W2092235133 cites W2150909784 @default.
• W2092235133 cites W2159413732 @default.
• W2092235133 cites W2162075350 @default.
• W2092235133 cites W2169290377 @default.
• W2092235133 cites W2170019668 @default.
• W2092235133 cites W2171992248 @default.
• W2092235133 cites W2183670135 @default.
• W2092235133 doi "https://doi.org/10.1371/journal.pone.0044363" @default.
• W2092235133 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3431376" @default.
• W2092235133 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22952966" @default.
• W2092235133 hasPublicationYear "2012" @default.
• W2092235133 type Work @default.
• W2092235133 sameAs 2092235133 @default.
• W2092235133 citedByCount "29" @default.
• W2092235133 countsByYear W20922351332013 @default.
• W2092235133 countsByYear W20922351332014 @default.
• W2092235133 countsByYear W20922351332015 @default.
• W2092235133 countsByYear W20922351332016 @default.

• next