Je. Radford et al., STIMULATION OF MHC CLASS-I TRANSCRIPTION BY INTERFERON-GAMMA INVOLVESA NON-A, NON-C KINASE IN ADDITION TO PROTEIN-KINASE-C, Journal of interferon research, 13(2), 1993, pp. 133-141
The signal pathways by which interferon-gamma (IFN-gamma) is able to u
p-regulate major histocompatibility complex (MHC) class I transcriptio
n were studied in two human hematopoietic tumor cell lines, K562 and R
amos. These studies suggest that the IFN-gamma signal is transduced vi
a an H7- and staurosporine-sensitive kinase that is distinct from prot
ein kinase C (PKC) and protein kinase A (PKA) in both cell types. Ramo
s cells appear to utilize an additional pathway involving double-stran
ded RNA-dependent protein kinase. PKC and possibly PKA appear to be in
volved in one or more intersecting pathways by which agonists of these
kinases are able to act synergistically with IFN-gamma, but activatio
n of these latter pathways is neither necessary nor sufficient for ind
uction of MHC class I transcription. Modulation of G-protein- and Ca2-calmodulin-associated pathways and arachidonic acid metabolism had no
effect on constitutive or IFN-gamma-stimulated class I transcription.
The class I stimulatory factor produced in response to IFN-gamma trea
tment appears to have a short t1/2. The identity of this factor is unk
nown, but is likely to be distinct from known mediators of IFN-stimula
ted transcription. Gene and cell-type specificity in the signal transd
uction pathways utilized by IFN-gamma implies that such pathways may b
e useful targets for experimental and therapeutic manipulation.