JAK2 is associated with the c-kit proto-oncogene product and is phosphorylated in response to stem cell factor.
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.
Weiler
S R
SR
Division of Cancer Treatment, and Biological Carcinogenesis and Development Program, SAIC Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702, USA.
Mou
S
S
DeBerry
C S
CS
Keller
J R
JR
Ruscetti
F W
FW
Ferris
D K
DK
Longo
D L
DL
Linnekin
D
D
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D006801:Humans; D053614:Janus Kinase 2; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D019089:Stem Cell Factor / Q000494:pharmacology*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D019089:Stem Cell Factor; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit; C507924:JAK2 protein, human; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2