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001-es BibID:BIBFORM069283
035-os BibID:(Cikkazonosító)34280 (WOS)000385169900001 (Scopus)84990245095
Első szerző:Dülk, Metta
Cím:The scaffold protein Tks4 is required for the differentiation of mesenchymal stromal cells (MSCs) into adipogenic and osteogenic lineages / Dülk Metta, Kudlik Gyöngyi, Fekete Anna, Ernszt Dávid, Kvell Krisztián, Pongrácz Judit E., Merő Balázs L., Szeder Bálint, Radnai László, Geiszt Miklós, Csécsy Dalma E., Kovács Tamás, Uher Ferenc, Lányi Árpád, Vas Virag, Buday László
Dátum:2016
ISSN:2045-2322
Megjegyzések:The protein product of the SH3PXD2B gene is known as Tks4 (tyrosine kinase substrate with 4 SH3 domains)6,a scaffold protein. Upon phosphorylation by Src kinase, it has the ability to interact with signaling molecules toregulate the actin cytoskeleton7. Tks4 was also shown to play an important role in the formation of podosomes8,production of reactive oxygen species (ROS) by tumor cells9, and also involved in EGFR signaling10,11. Althoughwe have some knowledge of the possible function of Tks4, the detailed mechanism of how Tks4 impacts FTHSaffected tissues is less clear.Mesenchymal stromal cells (MSCs) as multipotent adult stem cells are able to form multiple cell types ofmesenchymal origin, e.g. adipocytes and osteoblasts12,13, therefore it is tempting to speculate that Tks4 may affectosteogenesis and lipogenesis of MSCs. Moreover, there are some hints for the possible role of Tks4 in MSC biology.For example, membrane type-1 matrix metalloproteinase (MT1-MMP), which is a binding partner of Tks4,is known to play a role in MSCs differentiation and trafficking14. Moreover, it has been described that Tks4 isinvolved in ROS production and ROS modulates several signaling pathways regulating MSC differentiation15.Therefore, we hypothesized that Tks4 may play a role in the process necessary for MSC differentiation and oneof the underlying mechanisms causing the FTHS phenotype could be the impaired stem cell functions of Tks4deficient MSCs.Here we present a novel Tks4?/? mouse strain on C57Bl/6 background with the complete loss of Tks4 protein.The adult Tks4 deficient mice have reduced fat tissue mass and altered craniofacial and skeletal bones. Wecompared the phenotype and differentiation potential of BM-MSCs (bone marrow mesenchymal stromal cells)isolated from Tks4?/? and wild type mice. Our data demonstrate that in the absence of Tks4, adipogenic and osteogenicdifferentiation of BM-MSCs is impaired; therefore, we concluded that Tks4 is necessary for the adipogenicand osteogenic mesenchymal differentiation pathways.
Tárgyszavak:Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Tks4
adipogenesis
osteogenesis
mesenchymal differentiation
Megjelenés:Scientific Reports. - 6 : 1 (2016), p. 1-9. -
További szerzők:Kudlik Gyöngyi Fekete Anna Ernszt Dávid Kvell Krisztián Pongrácz Judit Merő Balázs L. Szeder Bálint Radnai László Geiszt Miklós Csécsy Dalma E. Kovács Tamás (Budapest) Uher Ferenc Lányi Árpád (1962-) (biológus, immunológus) Vas Virág Buday László
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