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JAK2 is associated with the c-kit proto-oncogene product and is phosphorylated in response to stem cell factor
S R Weiler1, S Mou, C S DeBerry
1Division of Cancer Treatment, and Biological Carcinogenesis and Development Program, SAIC Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702, USA.
Abstract:
Stem cell factor (SCF) is a hematopoietic growth factor that interacts with the receptor tyrosine kinase, c-kit. We have found that SCF-stimulates rapid and transient tyrosine phosphorylation of JAK2 in human and murine cell lines, as well as in normal human progenitor cells. JAK2 and c-kit were associated in unstimulated cells with further recruitment of JAK2 to the c-kit receptor complex after SCF stimulation. Treatment of cells with JAK2 antisense oligonucleotides resulted in a 46% decrease in SCF-induced proliferation. These data demonstrate that SCF induces tyrosine phosphorylation of JAK2 and suggest that JAK2 is a component of the SCF signal transduction pathway.
Insights
Stem cell factor (SCF) signaling involves Janus kinase 2 (JAK2) phosphorylation. This study shows JAK2 is crucial for SCF-induced cell proliferation, highlighting its role in the SCF pathway.
Area of Science:
- Hematology
- Cell signaling
- Molecular biology
Background:
- Stem cell factor (SCF) is a key hematopoietic growth factor.
- SCF interacts with the c-kit receptor tyrosine kinase.
- Understanding SCF signaling is vital for hematopoiesis research.
Purpose of the Study:
- To investigate the role of Janus kinase 2 (JAK2) in SCF signal transduction.
- To determine if JAK2 is involved in SCF-mediated cellular responses.
Main Methods:
- Utilized human and murine cell lines and normal human progenitor cells.
- Analyzed SCF-stimulated tyrosine phosphorylation of JAK2.
- Examined the association of JAK2 with the c-kit receptor complex.
- Employed JAK2 antisense oligonucleotides to assess proliferation.
Main Results:
- SCF stimulation induced rapid and transient tyrosine phosphorylation of JAK2.
- JAK2 was found to associate with c-kit, with increased recruitment upon SCF stimulation.
- JAK2 antisense oligonucleotides significantly reduced SCF-induced proliferation by 46%.
Conclusions:
- SCF induces tyrosine phosphorylation of JAK2.
- JAK2 is an integral component of the SCF signal transduction pathway.
- JAK2 plays a critical role in SCF-driven cellular proliferation.