Requirement of Src kinase Lyn for induction of DNA synthesis by granulocyte colony-stimulating factor.
J Biol Chem
; 273(6): 3230-5, 1998 Feb 06.
Article
in En
| MEDLINE
| ID: mdl-9452436
ABSTRACT
Treatment of cells with granulocyte colony-stimulating factor (G-CSF) leads to tyrosine phosphorylation of cellular proteins. G-CSF stimulates both the activation of protein tyrosine kinases Lyn, Jak1, and Jak2 and the association of these enzymes with the G-CSF receptor. Wild-type, lyn-deficient, and syk-deficient chicken B lymphocyte cell lines were transfected with the human G-CSF receptor, and stable transfectants were studied. G-CSF-dependent tyrosyl phosphorylation of Jak1 and Jak2 occurred in all three cell lines. Wild-type and syk-deficient transfectants responded to G-CSF in a dose-responsive fashion with increased thymidine incorporation, but none of the clones of lyn-deficient transfectants did. Ectopic expression of Lyn, but not that of c-Src, in the lyn-deficient cells restored their mitogenic responsiveness to G-CSF. Ectopic expression in wild-type cells of the kinase-inactive form of Lyn, but not of the kinase-inactive form of Jak2, inhibited thymidine incorporation in response to G-CSF. These studies show that the absence of Lyn results in the loss of mitogenic signaling in the G-CSF signaling pathway and that activation of Jak1 or Jak2 is not sufficient to cause mitogenesis.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Granulocyte Colony-Stimulating Factor
/
Proto-Oncogene Proteins
/
Src-Family Kinases
/
DNA Replication
Limits:
Animals
/
Humans
Language:
En
Journal:
J Biol Chem
Year:
1998
Document type:
Article
Affiliation country:
United States