Multiple
kinase events, involving both
tyrosine (tyr)
kinase and
serine/
threonine (ser/thr)
kinase activity, are required for IFN-gamma-induced class II MHC
mRNA and
protein expression in primary rat astrocytes. In this study, we examined the necessity of ser/thr and tyr
kinase activity for IFN-gamma-induced stimulation of class II MHC gene expression in the human
astroglioma cell lines CRT and CH235, as well as the involvement of these
kinases in IFN-gamma-induced expression of the
class II transactivator (CIITA), a
protein critical for IFN-gamma-induced transcription of class II MHC genes. We show that general ser/thr
kinase inhibitors, inhibitors of the ser/thr
kinase mitogen-activated protein kinase (MAPK), and tyr
kinase inhibitors reduce IFN-gamma-induced class II MHC
mRNA and
protein expression in a dose-dependent manner. As well, these inhibitors abrogate IFN-gamma-induced CIITA
mRNA expression in the
astroglioma cell lines. We have further demonstrated that cells constitutively expressing the CIITA
protein (2fTGH.CIITA) show no decrease in CIITA or class II MHC
mRNA expression in the presence of ser/thr and tyr
kinase inhibitors. Collectively, these data indicate that ser/thr
kinase activity, possibly MAPK, and tyr
kinase activity are required for IFN-gamma-induced expression of CIITA
mRNA, and the subsequent expression of class II MHC genes.