MAP kinase is constitutively activated in gip2 and src transformed rat 1a fibroblasts.
Rat 1a fibroblasts transformed by the Gi2 oncogene, gip2, exhibit a constitutively elevated mitogen-activated protein (MAP) kinase activity that correlates with enhanced tyrosine phosphorylation of the p42 MAP kinase polypeptide. The MAP kinase activity in gip2 transformed cells is 50-60% of the pertussis toxin-sensitive, thrombin-stimulated activity observed in wild-type Rat 1a cells. A similar activation of MAP kinase is observed in src but not ras or raf transformed Rat 1a cells, indicating that the persistent MAP kinase activity results from the action of the specific oncoprotein and is not the consequence of cellular transformation. The enhanced transactivation function of c-Jun characteristic of the transformed phenotype, measured using a collagenase promoter-CAT reporter gene, is observed in gip2, src, ras, and raf transformed Rat 1a cells. The regulatory networks controlled by the four transforming oncogenes therefore alter the activity of specific transcription factors, but only gip2 and src constitutively activate MAP kinase. The findings demonstrate that the catalytic activity of growth factor-regulated cytoplasmic kinases are selectively and stably activated as a consequence of specific oncogene expression.
Gupta
S K
SK
Division of Basic Sciences, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206.
Gallego
C
C
Johnson
G L
GL
Heasley
L E
LE
D000818:Animals; D015153:Blotting, Western; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002461:Cell Line, Transformed; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004789:Enzyme Activation; D005347:Fibroblasts / Q000201:enzymology; D019204:GTP-Binding Proteins / Q000235:genetics*; D011905:Genes, ras; D016391:Genes, src; D003012:Microbial Collagenase / Q000235:genetics; D015688:Oncogene Protein pp60(v-src) / Q000235:genetics*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D014443:Tyrosine / Q000378:metabolism
D016755:Proto-Oncogene Proteins c-jun; D014443:Tyrosine; D015500:Chloramphenicol O-Acetyltransferase; D011494:Protein Kinases; D015688:Oncogene Protein pp60(v-src); D017871:Calcium-Calmodulin-Dependent Protein Kinases; D003012:Microbial Collagenase; D019204:GTP-Binding Proteins