Mitogen-activated protein kinase activation resulting from selective oncogene expression in NIH 3T3 and rat 1a cells.
Mitogen-activated protein kinases (MAPKs) are serine/threonine kinases that are rapidly activated in response to a variety of growth factors in many cell types. MAPKs are activated by phosphorylation of both tyrosine and threonine residues. They are proposed to be key integrators of growth factor receptor transduction systems involving conversion of tyrosine kinase signals to serine/threonine kinase activation. We have studied the influence of specific oncogenes on the regulation of MAPK activity in NIH 3T3 and Rat 1a fibroblasts. In NIH 3T3 cells, ras or raf oncogene expression, but not gip2 oncogene expression, induces a significant constitutive MAPK activation. In contrast, in Rat 1a cells, gip2, but not ras or raf oncogene expression, induces a strong constitutive MAPK activation. The findings indicate that, in a cell type-selective manner, different oncoproteins are capable of causing the constitutive activation of MAPK. However, the magnitude of oncogene-induced MAPK activation is not directly correlated with cellular transformation in either cell type. It appears that expression of only a subset of transforming oncogenes in a specific cell type is able to alter the regulation of the MAPK activation pathway. Thus, the network of cytoplasmic serine/threonine kinases will be differentially regulated when the same oncogene is expressed in different cell types.
Gallego
C
C
Division of Basic Sciences, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Gupta
S K
SK
Heasley
L E
LE
Qian
N X
NX
Johnson
G L
GL
D016475:3T3 Cells; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002460:Cell Line; D004261:DNA Replication; D004789:Enzyme Activation; D015870:Gene Expression; D016758:Genes, jun; D011905:Genes, ras; D051379:Mice; D027384:Oncogene Proteins v-raf; D009857:Oncogenes; D011494:Protein Kinases / Q000302:isolation & purification / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D051381:Rats; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D015682:Retroviridae Proteins, Oncogenic; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D027384:Oncogene Proteins v-raf; D017871:Calcium-Calmodulin-Dependent Protein Kinases