Matches in SemOpenAlex for { <https://semopenalex.org/work/W3089746615> ?p ?o ?g. }
- W3089746615 endingPage "502.e18" @default.
- W3089746615 startingPage "490" @default.
- W3089746615 abstract "The non-receptor protein tyrosine phosphatase (PTP) SHP2, encoded by PTPN11, plays an essential role in RAS-mitogen-activated protein kinase (MAPK) signaling during normal development. It has been perplexing as to why both enzymatically activating and inactivating mutations in PTPN11 result in human developmental disorders with overlapping clinical manifestations. Here, we uncover a common liquid-liquid phase separation (LLPS) behavior shared by these disease-associated SHP2 mutants. SHP2 LLPS is mediated by the conserved well-folded PTP domain through multivalent electrostatic interactions and regulated by an intrinsic autoinhibitory mechanism through conformational changes. SHP2 allosteric inhibitors can attenuate LLPS of SHP2 mutants, which boosts SHP2 PTP activity. Moreover, disease-associated SHP2 mutants can recruit and activate wild-type (WT) SHP2 in LLPS to promote MAPK activation. These results not only suggest that LLPS serves as a gain-of-function mechanism involved in the pathogenesis of SHP2-associated human diseases but also provide evidence that PTP may be regulated by LLPS that can be therapeutically targeted." @default.
- W3089746615 created "2020-10-08" @default.
- W3089746615 creator A5001014826 @default.
- W3089746615 creator A5002509398 @default.
- W3089746615 creator A5009590736 @default.
- W3089746615 creator A5009783386 @default.
- W3089746615 creator A5019069494 @default.
- W3089746615 creator A5025734647 @default.
- W3089746615 creator A5034188355 @default.
- W3089746615 creator A5035853333 @default.
- W3089746615 creator A5037202985 @default.
- W3089746615 creator A5038851564 @default.
- W3089746615 creator A5045157829 @default.
- W3089746615 creator A5054176992 @default.
- W3089746615 creator A5058342706 @default.
- W3089746615 creator A5059076044 @default.
- W3089746615 creator A5059881584 @default.
- W3089746615 creator A5063484575 @default.
- W3089746615 creator A5065863457 @default.
- W3089746615 creator A5065892182 @default.
- W3089746615 creator A5066128641 @default.
- W3089746615 creator A5066546362 @default.
- W3089746615 creator A5066908799 @default.
- W3089746615 creator A5067025277 @default.
- W3089746615 creator A5084065650 @default.
- W3089746615 creator A5085848424 @default.
- W3089746615 date "2020-10-01" @default.
- W3089746615 modified "2023-10-18" @default.
- W3089746615 title "Phase Separation of Disease-Associated SHP2 Mutants Underlies MAPK Hyperactivation" @default.
- W3089746615 cites W1599373893 @default.
- W3089746615 cites W1674292201 @default.
- W3089746615 cites W1963770414 @default.
- W3089746615 cites W1969918683 @default.
- W3089746615 cites W1985188811 @default.
- W3089746615 cites W2000523053 @default.
- W3089746615 cites W2000813775 @default.
- W3089746615 cites W2009086159 @default.
- W3089746615 cites W2010137154 @default.
- W3089746615 cites W2015964672 @default.
- W3089746615 cites W2047534842 @default.
- W3089746615 cites W2051209422 @default.
- W3089746615 cites W2058398046 @default.
- W3089746615 cites W2080822958 @default.
- W3089746615 cites W2081439838 @default.
- W3089746615 cites W2082813362 @default.
- W3089746615 cites W2084440639 @default.
- W3089746615 cites W2085978470 @default.
- W3089746615 cites W2092800497 @default.
- W3089746615 cites W2113349387 @default.
- W3089746615 cites W2124171936 @default.
- W3089746615 cites W2130526419 @default.
- W3089746615 cites W2135745763 @default.
- W3089746615 cites W2138697615 @default.
- W3089746615 cites W2143747124 @default.
- W3089746615 cites W2144844081 @default.
- W3089746615 cites W2145466141 @default.
- W3089746615 cites W2159532830 @default.
- W3089746615 cites W2165869860 @default.
- W3089746615 cites W2168639701 @default.
- W3089746615 cites W2168958678 @default.
- W3089746615 cites W2169365832 @default.
- W3089746615 cites W2235833515 @default.
- W3089746615 cites W2258447134 @default.
- W3089746615 cites W2335345046 @default.
- W3089746615 cites W2468923062 @default.
- W3089746615 cites W2541514381 @default.
- W3089746615 cites W2553996574 @default.
- W3089746615 cites W2590568317 @default.
- W3089746615 cites W2756821926 @default.
- W3089746615 cites W2782130029 @default.
- W3089746615 cites W2791036684 @default.
- W3089746615 cites W2795445828 @default.
- W3089746615 cites W2801688422 @default.
- W3089746615 cites W2803177876 @default.
- W3089746615 cites W2809609078 @default.
- W3089746615 cites W2854081253 @default.
- W3089746615 cites W2898146177 @default.
- W3089746615 cites W2914907359 @default.
- W3089746615 cites W2921733160 @default.
- W3089746615 cites W2969279439 @default.
- W3089746615 doi "https://doi.org/10.1016/j.cell.2020.09.002" @default.
- W3089746615 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7572904" @default.
- W3089746615 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33002410" @default.
- W3089746615 hasPublicationYear "2020" @default.
- W3089746615 type Work @default.
- W3089746615 sameAs 3089746615 @default.
- W3089746615 citedByCount "107" @default.
- W3089746615 countsByYear W30897466152021 @default.
- W3089746615 countsByYear W30897466152022 @default.
- W3089746615 countsByYear W30897466152023 @default.
- W3089746615 crossrefType "journal-article" @default.
- W3089746615 hasAuthorship W3089746615A5001014826 @default.
- W3089746615 hasAuthorship W3089746615A5002509398 @default.
- W3089746615 hasAuthorship W3089746615A5009590736 @default.
- W3089746615 hasAuthorship W3089746615A5009783386 @default.
- W3089746615 hasAuthorship W3089746615A5019069494 @default.
- W3089746615 hasAuthorship W3089746615A5025734647 @default.
- W3089746615 hasAuthorship W3089746615A5034188355 @default.