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The Csk-binding protein PAG regulates PDGF-induced Src mitogenic signaling via GM1

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F08%3A00315261" target="_blank" >RIV/68378050:_____/08:00315261 - isvavai.cz</a>

  • Result on the web

  • DOI - Digital Object Identifier

Alternative languages

  • Result language

    angličtina

  • Original language name

    The Csk-binding protein PAG regulates PDGF-induced Src mitogenic signaling via GM1

  • Original language description

    Cholesterol-enriched membrane domains, such as caveolae, regulate association of SRC family protein tyrosine kinases (SFK) with the platelet-derived growth factor receptor (PDGFR), which is needed for mitogenic signaling. PAG, a ubiquitously expressed member of the transmembrane adaptor protein family, is known to negatively regulate SFK signaling though binding to Csk. PAG was found to modulate PDGFR levels in caveolae and SFK mitogenic signaling through a Csk-independent mechanism. Regulation of SFK mitogenic activity by PAG requires the first N-terminal 97 aa (PAG-N), which include the extracellular and transmembrane domains, palmitoylation sites, and a short cytoplasmic sequence. PAG-N increases ganglioside GM1 levels at the cell surface and, thus,displaces PDGFR from caveolae, a process that requires the ganglioside-specific sialidase Neu-3. PAG regulates PDGFR membrane partitioning and SFK mitogenic signaling by modulating GM1 levels within caveolae independently from Csk.

  • Czech name

    Csk-vážící protein PAG reguluje Src-indukovanou mitogenní signalizaci PDGF via GM1

  • Czech description

    Membránové mikrodomény obohacené cholesterolem, jako jsou caveoly, regulují asociaci protein kinas rodiny Src (SFK) s PDGF-receptorem (PDGFR), která je potřebná pro mitogenní signalizaci. PAG, široce exprimovaný transmembránový adaptorový protein, negativně reguluje SFK tím, že váže a aktivuje kinasu Csk. Bylo zjištěno, že PAG moduluje množství PRGFR v caveolách a mitogenní signalizaci pomocí mechanismu nezávislého na Csk. Tato regulace vyžaduje prvních N-terminálních 97 aa PAG 9PAG-N). PAG-N zvyšuje množství gangliosidu GM1 na buněčném povrchu a vytěsňuje GM1 z caveol. Tento proces vyžaduje sialidasu Neu-3. PAG tedy reguluje distribuci PDGFR a mitogenní aktivitu SFK tím, že moduluje GM1 v caveolách nezávisle na Csk.

Classification

  • Type

    J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

  • CEP classification

    EB - Genetics and molecular biology

  • OECD FORD branch

Result continuities

  • Project

    <a href="/en/project/1M0506" target="_blank" >1M0506: Center of Molecular and Cellular Immunology</a><br>

  • Continuities

    Z - Vyzkumny zamer (s odkazem do CEZ)

Others

  • Publication year

    2008

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Journal of Cell Biology

  • ISSN

    0021-9525

  • e-ISSN

  • Volume of the periodical

    182

  • Issue of the periodical within the volume

    3

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    12

  • Pages from-to

  • UT code for WoS article

    000258529100018

  • EID of the result in the Scopus database