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Centrosomal targeting of tyrosine kinase activity does not enhance oncogenicity in chronic myeloproliferative disorders

Constitutive tyrosine kinase activation by reciprocal chromosomal translocation is a common pathogenetic mechanism in chronic myeloproliferative disorders. Since centrosomal proteins have been recurrently identified as translocation partners of tyrosine kinases FGFR1, JAK2, PDGFRα and PDGFRβ in thes...

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Hauptverfasser: Bochtler, Tilmann (VerfasserIn) , Kirsch, Michael (VerfasserIn) , Klingmüller, Ursula (VerfasserIn) , Ho, Anthony Dick (VerfasserIn) , Krämer, Alwin (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2012
In: Leukemia
Year: 2012, Jahrgang: 26, Heft: 4, Pages: 728-735
ISSN:1476-5551
DOI:10.1038/leu.2011.283
Online-Zugang:Verlag, Volltext: http://dx.doi.org/10.1038/leu.2011.283
Verlag, Volltext: https://www.nature.com/articles/leu2011283
Volltext
Verfasserangaben:T Bochtler, M Kirsch, B Maier, J Bachmann, U Klingmüller, S Anderhub, AD Ho and A Krämer
Beschreibung
Zusammenfassung:Constitutive tyrosine kinase activation by reciprocal chromosomal translocation is a common pathogenetic mechanism in chronic myeloproliferative disorders. Since centrosomal proteins have been recurrently identified as translocation partners of tyrosine kinases FGFR1, JAK2, PDGFRα and PDGFRβ in these diseases, a role for the centrosome in oncogenic transformation has been hypothesized. In this study, we addressed the functional role of centrosomally targeted tyrosine kinase activity. First, centrosomal localization was not routinely found for all chimeric fusion proteins tested. Second, targeting of tyrosine kinases to the centrosome by creating artificial chimeric fusion kinases with the centrosomal targeting domain of AKAP450 failed to enhance the oncogenic transforming potential in both Ba/F3 and U2OS cells, although phospho-tyrosine-mediated signal transduction pathways were initiated at the centrosome. We conclude that the centrosomal localization of constitutively activated tyrosine kinases does not contribute to disease pathogenesis in chronic myeloproliferative disorders.
Beschreibung:Gesehen am 11.10.2018
Published online 21 October 2011
Beschreibung:Online Resource
ISSN:1476-5551
DOI:10.1038/leu.2011.283

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