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Reduced expression of SRC family kinases decreases PI3K activity in NBS1-/- lymphoblasts.
Biochem. Biophys. Res. Commun. 377, 181-186 (2008)
SRC family kinases (SFKs) are involved in the activation of phosphatidylinositol-3-kinase (PI3K). In addition, the activity of this lipid kinase can be regulated by the DNA repair protein NBS1. Here, we describe a disturbed expression of some members of the non-receptor tyrosine kinase family in lymphoblastoid cell lines generated from cells of Nijmegen breakage syndrome (NBS) patients. Especially, only minor amounts of the kinases LCK and HCK are expressed in the NBS1(-/-) cell lines as compared to the consanguineous NBS1(+/-) cells. We demonstrate that SFK activity is important for a proper activation of PI3K in these cells and that it is reduced in NBS1(-/-) cells. We provide evidence that the observed reduced PI3K activity in NBS lymphoblasts is caused by an impaired expression of the SFKs LCK and/or HCK. Thus, our data establish a new function for the NBS1 protein as a regulator of PI3K activity via SFK members.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
PI3K; NBS1; SFK; LCK; HCK
ISSN (print) / ISBN
0006-291X
e-ISSN
1090-2104
Quellenangaben
Band: 377,
Heft: 1,
Seiten: 181-186
Verlag
Elsevier
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Radiation Biology (ISB)