Activation of the pp90rsk and mitogen-activated serine/threonine protein kinases by ionizing radiation.
The cellular response to ionizing radiation (IR) includes induction of the c-jun and EGR1 early response genes. The present work has examined potential cytoplasmic signaling cascades that transduce IR-induced signals to the nucleus. The results demonstrate activation of the 40S ribosomal protein S6 kinase, pp90rsk, in human U-937 myeloid leukemia cells. Partial purification of pp90rsk by affinity chromatography demonstrated an increase in S6 peptide phosphorylation when comparing irradiated with control cells. IR-induced activation of pp90rsk was further confirmed in immune-complex kinase assays. In contrast to these findings, there was no detectable induction of pp70S6K. Previous work has demonstrated that mitogen-activated protein kinase activates pp90rsk. The present results further show that IR treatment is associated with induction of mitogen-activated protein kinase activity and that this event is temporally related to activation of pp90rsk and early response gene expression. These findings suggest that activation of the mitogen-activated protein kinase/pp90rsk cascade is involved in the response of cells to IR exposure.
Kharbanda
S
S
Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Saleem
A
A
Shafman
T
T
Emoto
Y
Y
Weichselbaum
R
R
Kufe
D
D
D001483:Base Sequence; D002460:Cell Line; D004789:Enzyme Activation / Q000528:radiation effects; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000528:radiation effects*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism / Q000528:radiation effects*; D011839:Radiation, Ionizing; D012045:Regulatory Sequences, Nucleic Acid; D019893:Ribosomal Protein S6 Kinases
D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases; D019950:Mitogen-Activated Protein Kinase 1