Regulation by EGF is maintained in an overexpressed chimeric EGFR/neu receptor tyrosine kinase.
The effects of a ligand regulated neu tyrosine kinase were examined in NIH 3T3 cells. A chimeric construct encoding the human EGF receptor extracellular domain fused to the tyrosine kinase domain of the rat neu cDNA was expressed under the transcriptional control of the Moloney murine leukemia virus LTR promoter. This resulted in higher levels of expression of the chimeric receptor than were previously obtained from the SV40 virus early promoter in the same cells. The chimeric receptor showed strict ligand-dependent tyrosine kinase and signal transducing activities for the induction of growth-regulated biochemical activities and DNA synthesis in resting cells. The ligand-activated cells became morphologically transformed and grew in agar in the presence of EGF and TGF beta as efficiently as did the ligand-independent neu oncogene-transformed cells. Our results establish similarities between the signal pathways of the EGF receptor and the neu tyrosine kinase.
Lehväslaiho
H
H
Department of Virology, University of Helsinki, Finland.
Sistonen
L
L
diRenzo
F
F
Partanen
J
J
Comoglio
P
P
Hölttä
E
E
Alitalo
K
K
D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D004815:Epidermal Growth Factor / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D006801:Humans; D051379:Mice; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases; D015398:Signal Transduction; D014170:Transformation, Genetic; D015291:Transforming Growth Factors / Q000494:pharmacology
D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D005947:Glucose; D009955:Ornithine Decarboxylase; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D015291:Transforming Growth Factors