Stem cell factor (SCF) and its tyrosine kinase receptor, c-Kit, play a cruc
ial role in regulating migration and proliferation of melanoblasts, germ ce
lls, and hemopoietic cell progenitors by activating a number of intracellul
ar signaling molecules. Here we report that SCF stimulation of myeloid cell
s or fibroblasts ectopically expressing c-Kit induces physical association
with and tyrosine phosphorylation of three signal transducers and activator
s of transcription (STATs) as follows: STAT1 alpha, STAT5A, and STAT5B. Oth
er STAT proteins are not recruited upon SCF stimulation. Recruitment of STA
Ts leads to their dimerization, nuclear translocation, and binding to speci
fic promoter-responsive elements. Whereas STAT1 alpha, possibly in the form
of homodimers, binds to the sis-inducible DNA element, STAT5 proteins, eit
her as STAT5A/STAT5B or STAT5/STAT1 alpha heterodimers, bind to the prolact
in-inducible element of the beta-casein promoter. The tyrosine kinase activ
ity of Kit appears essential for STAT activation since a kinase-defective m
utant lacking a kinase insert domain was inactive in STAT signaling. Howeve
r, another mutant that lacked the carboxyl-terminal region retained STAT1 a
lpha activation and nuclear translocation but was unable to fully activate
STATE proteins, although it mediated their transient phosphorylation, These
results indicate that different intracellular domains of c-Kit are involve
d in activation of the various STAT proteins.