We are analyzing https://link.springer.com/article/10.1007/s00018-023-05052-8.

Title:
SHP2 clinical phenotype, cancer, or RASopathies, can be predicted by mutant conformational propensities | Cellular and Molecular Life Sciences
Description:
SHP2 phosphatase promotes full activation of the RTK-dependent Ras/MAPK pathway. Its mutations can drive cancer and RASopathies, a group of neurodevelopmental disorders (NDDs). Here we ask how same residue mutations in SHP2 can lead to both cancer and NDD phenotypes, and whether we can predict what the outcome will be. We collected and analyzed mutation data from the literature and cancer databases and performed molecular dynamics simulations of SHP2 mutants. We show that both cancer and Noonan syndrome (NS, a RASopathy) mutations favor catalysis-prone conformations. As to cancer versus RASopathies, we demonstrate that cancer mutations are more likely to accelerate SHP2 activation than the NS mutations at the same genomic loci, in line with NMR data for K-Ras4B more aggressive mutations. The compiled experimental data and dynamic features of SHP2 mutants lead us to propose that different from strong oncogenic mutations, SHP2 activation by NS mutations is less likely to induce a transition of the ensemble from the SHP2 inactive state to the active state. Strong signaling promotes cell proliferation, a hallmark of cancer. Weak, or moderate signals are associated with differentiation. In embryonic neural cells, dysregulated differentiation is connected to NDDs. Our innovative work offers structural guidelines for identifying and correlating mutations with clinical outcomes, and an explanation for why bearers of RASopathy mutations may have a higher probability of cancer. Finally, we propose a drug strategy against SHP2 variants-promoting cancer and RASopathies.
Website Age:
28 years and 1 months (reg. 1997-05-29).

Matching Content Categories {📚}

Education
Health & Fitness
Science

Content Management System {📝}

What CMS is link.springer.com built with?

Custom-built

No common CMS systems were detected on Link.springer.com, and no known web development framework was identified.

Traffic Estimate {📈}

What is the average monthly size of link.springer.com audience?

🌠 Phenomenal Traffic: 5M - 10M visitors per month

Based on our best estimate, this website will receive around 5,000,019 visitors per month in the current month.
However, some sources were not loaded, we suggest to reload the page to get complete results.

check SE Ranking
check Ahrefs
check Similarweb
check Ubersuggest
check Semrush

How Does Link.springer.com Make Money? {💸}

We don't see any clear sign of profit-making.

Not every website is profit-driven; some are created to spread information or serve as an online presence. Websites can be made for many reasons. This could be one of them. Link.springer.com could be getting rich in stealth mode, or the way it's monetizing isn't detectable.

Keywords {🔍}

pubmed, article, google, scholar, cas, shp, cancer, central, mutations, ptpn, syndrome, allosteric, nussinov, phosphatase, genet, noonan, zhang, jang, activation, nat, chem, med, clinical, cell, sci, biol, leopard, molecular, liu, signaling, inhibition, tsai, leukemia, hum, data, mutation, tyrosine, gene, inhibitor, oncogenic, structural, res, commun, disorders, cancers, mutants, resistance, wang, chen, usa,

Topics {✒️}

rtk-dependent ras/mapk pathway month download article/chapter high-performance computational facilities n-sh2 binding cleft biowulf pc/linux cluster block ras-driven cancers ras-mapk pathway flt3-itd-driven aml dna damage-induced malignancies monomeric b-raf v600e cardio-facio-cutaneous syndrome oncogenic k-ras-gdp targeted cancer drugs full article pdf brain-restricted mtor inhibition measure signal transduction pan-cancer clinical impact maintains tumor-initiating cells mackerell ad jr shp2 variants-promoting cancer article liu ras-driven cancers pak1-regulated mapk mutant conformational propensities shp-2 tyrosine phosphatase ras suppresses oncogenesis brooks cl 3rd receptor tyrosine kinases protein–protein interactions protein-tyrosine phosphatase privacy choices/manage cookies allosteric inhibitor asciminib tyrosine phosphatase shp2 shp2 tyrosine phosphatase verkhivker gm allosteric shp2 inhibitor mek inhibitor cobimetinib shp2-mediated dephosphorylation juvenile myelomonocytic leukemia article cellular oncogenic phosphatase shp2 ras pathway fgfr-driven cancers simple binding domains mek inhibitor resistance dual allosteric inhibition central node acute myelomonocytic leukemia improved force field bengi ruken yavuz

Questions {❓}

Edouard T, Montagner A, Dance M, Conte F, Yart A, Parfait B et al (2007) How do Shp2 mutations that oppositely influence its biochemical activity result in syndromes with overlapping symptoms?
Nussinov R, Tsai C-J, Jang H (2019) Why are some driver mutations rare?
Nussinov R, Tsai CJ, Jang H (2022) How can same-gene mutations promote both cancer and developmental disorders?
Tomlinson I, Sasieni P, Bodmer W (2002) How many mutations in a cancer?

Schema {🗺️}

WebPage:
      mainEntity:
         headline:SHP2 clinical phenotype, cancer, or RASopathies, can be predicted by mutant conformational propensities
         description:SHP2 phosphatase promotes full activation of the RTK-dependent Ras/MAPK pathway. Its mutations can drive cancer and RASopathies, a group of neurodevelopmental disorders (NDDs). Here we ask how same residue mutations in SHP2 can lead to both cancer and NDD phenotypes, and whether we can predict what the outcome will be. We collected and analyzed mutation data from the literature and cancer databases and performed molecular dynamics simulations of SHP2 mutants. We show that both cancer and Noonan syndrome (NS, a RASopathy) mutations favor catalysis-prone conformations. As to cancer versus RASopathies, we demonstrate that cancer mutations are more likely to accelerate SHP2 activation than the NS mutations at the same genomic loci, in line with NMR data for K-Ras4B more aggressive mutations. The compiled experimental data and dynamic features of SHP2 mutants lead us to propose that different from strong oncogenic mutations, SHP2 activation by NS mutations is less likely to induce a transition of the ensemble from the SHP2 inactive state to the active state. Strong signaling promotes cell proliferation, a hallmark of cancer. Weak, or moderate signals are associated with differentiation. In embryonic neural cells, dysregulated differentiation is connected to NDDs. Our innovative work offers structural guidelines for identifying and correlating mutations with clinical outcomes, and an explanation for why bearers of RASopathy mutations may have a higher probability of cancer. Finally, we propose a drug strategy against SHP2 variants-promoting cancer and RASopathies.
         datePublished:2023-12-12T00:00:00Z
         dateModified:2023-12-12T00:00:00Z
         pageStart:1
         pageEnd:17
         sameAs:https://doi.org/10.1007/s00018-023-05052-8
         keywords:
            PTPN11
            Phosphatase
            Neurodevelopmental disorders
            Allosteric drugs
            Signaling
            Ras/MAPK pathway
            Bitopic inhibitor
            Cell Biology
            Biomedicine
            general
            Life Sciences
            Biochemistry
         image:
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00018-023-05052-8/MediaObjects/18_2023_5052_Fig1_HTML.png
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00018-023-05052-8/MediaObjects/18_2023_5052_Fig2_HTML.png
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00018-023-05052-8/MediaObjects/18_2023_5052_Fig3_HTML.png
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00018-023-05052-8/MediaObjects/18_2023_5052_Fig4_HTML.png
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00018-023-05052-8/MediaObjects/18_2023_5052_Fig5_HTML.png
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00018-023-05052-8/MediaObjects/18_2023_5052_Fig6_HTML.png
         isPartOf:
            name:Cellular and Molecular Life Sciences
            issn:
               1420-9071
               1420-682X
            volumeNumber:81
            type:
               Periodical
               PublicationVolume
         publisher:
            name:Springer International Publishing
            logo:
               url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
               type:ImageObject
            type:Organization
         author:
               name:Yonglan Liu
               affiliation:
                     name:National Cancer Institute
                     address:
                        name:Cancer Innovation Laboratory, National Cancer Institute, Frederick, USA
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Wengang Zhang
               affiliation:
                     name:National Cancer Institute
                     address:
                        name:Cancer Innovation Laboratory, National Cancer Institute, Frederick, USA
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Hyunbum Jang
               affiliation:
                     name:Frederick National Laboratory for Cancer Research
                     address:
                        name:Computational Structural Biology Section, Frederick National Laboratory for Cancer Research, Frederick, USA
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Ruth Nussinov
               url:http://orcid.org/0000-0002-8115-6415
               affiliation:
                     name:Frederick National Laboratory for Cancer Research
                     address:
                        name:Computational Structural Biology Section, Frederick National Laboratory for Cancer Research, Frederick, USA
                        type:PostalAddress
                     type:Organization
                     name:Sackler School of Medicine, Tel Aviv University
                     address:
                        name:Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
                        type:PostalAddress
                     type:Organization
               email:[email protected]
               type:Person
         isAccessibleForFree:
         hasPart:
            isAccessibleForFree:
            cssSelector:.main-content
            type:WebPageElement
         type:ScholarlyArticle
      context:https://schema.org
ScholarlyArticle:
      headline:SHP2 clinical phenotype, cancer, or RASopathies, can be predicted by mutant conformational propensities
      description:SHP2 phosphatase promotes full activation of the RTK-dependent Ras/MAPK pathway. Its mutations can drive cancer and RASopathies, a group of neurodevelopmental disorders (NDDs). Here we ask how same residue mutations in SHP2 can lead to both cancer and NDD phenotypes, and whether we can predict what the outcome will be. We collected and analyzed mutation data from the literature and cancer databases and performed molecular dynamics simulations of SHP2 mutants. We show that both cancer and Noonan syndrome (NS, a RASopathy) mutations favor catalysis-prone conformations. As to cancer versus RASopathies, we demonstrate that cancer mutations are more likely to accelerate SHP2 activation than the NS mutations at the same genomic loci, in line with NMR data for K-Ras4B more aggressive mutations. The compiled experimental data and dynamic features of SHP2 mutants lead us to propose that different from strong oncogenic mutations, SHP2 activation by NS mutations is less likely to induce a transition of the ensemble from the SHP2 inactive state to the active state. Strong signaling promotes cell proliferation, a hallmark of cancer. Weak, or moderate signals are associated with differentiation. In embryonic neural cells, dysregulated differentiation is connected to NDDs. Our innovative work offers structural guidelines for identifying and correlating mutations with clinical outcomes, and an explanation for why bearers of RASopathy mutations may have a higher probability of cancer. Finally, we propose a drug strategy against SHP2 variants-promoting cancer and RASopathies.
      datePublished:2023-12-12T00:00:00Z
      dateModified:2023-12-12T00:00:00Z
      pageStart:1
      pageEnd:17
      sameAs:https://doi.org/10.1007/s00018-023-05052-8
      keywords:
         PTPN11
         Phosphatase
         Neurodevelopmental disorders
         Allosteric drugs
         Signaling
         Ras/MAPK pathway
         Bitopic inhibitor
         Cell Biology
         Biomedicine
         general
         Life Sciences
         Biochemistry
      image:
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00018-023-05052-8/MediaObjects/18_2023_5052_Fig1_HTML.png
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00018-023-05052-8/MediaObjects/18_2023_5052_Fig2_HTML.png
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00018-023-05052-8/MediaObjects/18_2023_5052_Fig3_HTML.png
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00018-023-05052-8/MediaObjects/18_2023_5052_Fig4_HTML.png
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00018-023-05052-8/MediaObjects/18_2023_5052_Fig5_HTML.png
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00018-023-05052-8/MediaObjects/18_2023_5052_Fig6_HTML.png
      isPartOf:
         name:Cellular and Molecular Life Sciences
         issn:
            1420-9071
            1420-682X
         volumeNumber:81
         type:
            Periodical
            PublicationVolume
      publisher:
         name:Springer International Publishing
         logo:
            url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
            type:ImageObject
         type:Organization
      author:
            name:Yonglan Liu
            affiliation:
                  name:National Cancer Institute
                  address:
                     name:Cancer Innovation Laboratory, National Cancer Institute, Frederick, USA
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Wengang Zhang
            affiliation:
                  name:National Cancer Institute
                  address:
                     name:Cancer Innovation Laboratory, National Cancer Institute, Frederick, USA
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Hyunbum Jang
            affiliation:
                  name:Frederick National Laboratory for Cancer Research
                  address:
                     name:Computational Structural Biology Section, Frederick National Laboratory for Cancer Research, Frederick, USA
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Ruth Nussinov
            url:http://orcid.org/0000-0002-8115-6415
            affiliation:
                  name:Frederick National Laboratory for Cancer Research
                  address:
                     name:Computational Structural Biology Section, Frederick National Laboratory for Cancer Research, Frederick, USA
                     type:PostalAddress
                  type:Organization
                  name:Sackler School of Medicine, Tel Aviv University
                  address:
                     name:Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
                     type:PostalAddress
                  type:Organization
            email:[email protected]
            type:Person
      isAccessibleForFree:
      hasPart:
         isAccessibleForFree:
         cssSelector:.main-content
         type:WebPageElement
["Periodical","PublicationVolume"]:
      name:Cellular and Molecular Life Sciences
      issn:
         1420-9071
         1420-682X
      volumeNumber:81
Organization:
      name:Springer International Publishing
      logo:
         url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
         type:ImageObject
      name:National Cancer Institute
      address:
         name:Cancer Innovation Laboratory, National Cancer Institute, Frederick, USA
         type:PostalAddress
      name:National Cancer Institute
      address:
         name:Cancer Innovation Laboratory, National Cancer Institute, Frederick, USA
         type:PostalAddress
      name:Frederick National Laboratory for Cancer Research
      address:
         name:Computational Structural Biology Section, Frederick National Laboratory for Cancer Research, Frederick, USA
         type:PostalAddress
      name:Frederick National Laboratory for Cancer Research
      address:
         name:Computational Structural Biology Section, Frederick National Laboratory for Cancer Research, Frederick, USA
         type:PostalAddress
      name:Sackler School of Medicine, Tel Aviv University
      address:
         name:Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
         type:PostalAddress
ImageObject:
      url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
Person:
      name:Yonglan Liu
      affiliation:
            name:National Cancer Institute
            address:
               name:Cancer Innovation Laboratory, National Cancer Institute, Frederick, USA
               type:PostalAddress
            type:Organization
      name:Wengang Zhang
      affiliation:
            name:National Cancer Institute
            address:
               name:Cancer Innovation Laboratory, National Cancer Institute, Frederick, USA
               type:PostalAddress
            type:Organization
      name:Hyunbum Jang
      affiliation:
            name:Frederick National Laboratory for Cancer Research
            address:
               name:Computational Structural Biology Section, Frederick National Laboratory for Cancer Research, Frederick, USA
               type:PostalAddress
            type:Organization
      name:Ruth Nussinov
      url:http://orcid.org/0000-0002-8115-6415
      affiliation:
            name:Frederick National Laboratory for Cancer Research
            address:
               name:Computational Structural Biology Section, Frederick National Laboratory for Cancer Research, Frederick, USA
               type:PostalAddress
            type:Organization
            name:Sackler School of Medicine, Tel Aviv University
            address:
               name:Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Cancer Innovation Laboratory, National Cancer Institute, Frederick, USA
      name:Cancer Innovation Laboratory, National Cancer Institute, Frederick, USA
      name:Computational Structural Biology Section, Frederick National Laboratory for Cancer Research, Frederick, USA
      name:Computational Structural Biology Section, Frederick National Laboratory for Cancer Research, Frederick, USA
      name:Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
WebPageElement:
      isAccessibleForFree:
      cssSelector:.main-content

External Links {🔗}(448)

Analytics and Tracking {📊}

Google Tag Manager

Libraries {📚}

Clipboard.js
Prism.js

CDN Services {📦}

Crossref

5.06s.

LINK . SPRINGER . COM {}