TY - JOUR
T1 - Activation of the neu tyrosine kinase induces the fos/jun transcription factor complex, the glucose transporter and ornithine decarboxylase
AU - Sistonen, L
AU - Hölttä, E
AU - Lehväslaiho, H
AU - Lehtola, L
AU - Alitalo, K
PY - 1989/11
Y1 - 1989/11
N2 - We have studied the ability of the neu tyrosine kinase to induce a signal for the activation of cell growth-regulated genes. Serum-starved NIH 3T3 cells expressing an epidermal growth factor receptor (EGF-R)/neu construct encoding a hybrid receptor protein were stimulated with EGF and the activation of the neu tyrosine kinase and stimulation of growth factor inducible genes were followed at the mRNA, protein, and activity levels, and compared to the corresponding responses in the neu proto-oncogene and oncogene expressing cells. Induction of the expression of jun mRNAs was an immediate early effect of EGF stimulation, followed by a marked increase in the biosynthesis of the fos/jun transcription factor complex and an increased transcription factor activity as measured by a recombinant transcription unit using chloramphenicol acetyltransferase assays. In distinction, elevated AP-1/PEA-1 activity in the absence of a significant increase in jun and fos expression was characteristic of the neu oncogene-expressing cells. The glucose transporter mRNA increased at 2 h of EGF stimulation and was associated with enhanced glucose transport of the EGF-treated cells. An increase of ornithine decarboxylase (ODC) mRNA and activity followed these changes. In contrast, serum-starved, EGF-treated neu proto-oncogene- and oncogene-expressing cells showed constitutively low and high glucose transporter and ODC activities, respectively. These findings demonstrate that the chimeric EGF-R/neu receptor is capable of activating the expression of both immediate early genes and biochemical activities associated with cell growth stimulation.
AB - We have studied the ability of the neu tyrosine kinase to induce a signal for the activation of cell growth-regulated genes. Serum-starved NIH 3T3 cells expressing an epidermal growth factor receptor (EGF-R)/neu construct encoding a hybrid receptor protein were stimulated with EGF and the activation of the neu tyrosine kinase and stimulation of growth factor inducible genes were followed at the mRNA, protein, and activity levels, and compared to the corresponding responses in the neu proto-oncogene and oncogene expressing cells. Induction of the expression of jun mRNAs was an immediate early effect of EGF stimulation, followed by a marked increase in the biosynthesis of the fos/jun transcription factor complex and an increased transcription factor activity as measured by a recombinant transcription unit using chloramphenicol acetyltransferase assays. In distinction, elevated AP-1/PEA-1 activity in the absence of a significant increase in jun and fos expression was characteristic of the neu oncogene-expressing cells. The glucose transporter mRNA increased at 2 h of EGF stimulation and was associated with enhanced glucose transport of the EGF-treated cells. An increase of ornithine decarboxylase (ODC) mRNA and activity followed these changes. In contrast, serum-starved, EGF-treated neu proto-oncogene- and oncogene-expressing cells showed constitutively low and high glucose transporter and ODC activities, respectively. These findings demonstrate that the chimeric EGF-R/neu receptor is capable of activating the expression of both immediate early genes and biochemical activities associated with cell growth stimulation.
KW - Animals
KW - Cells, Cultured
KW - Culture Media
KW - Enzyme Activation
KW - Epidermal Growth Factor/pharmacology
KW - ErbB Receptors/metabolism
KW - Gene Expression Regulation
KW - Genes/drug effects
KW - Kinetics
KW - Mice
KW - Mice, Inbred Strains
KW - Monosaccharide Transport Proteins/biosynthesis
KW - Oncogenes
KW - Ornithine Decarboxylase/biosynthesis
KW - Protein-Tyrosine Kinases/metabolism
KW - Proto-Oncogene Proteins/genetics
KW - Receptor, ErbB-2
KW - Transcription Factors/biosynthesis
KW - Transcription, Genetic
U2 - 10.1083/jcb.109.5.1911
DO - 10.1083/jcb.109.5.1911
M3 - Article
C2 - 2572601
SN - 0021-9525
VL - 109
SP - 1911
EP - 1919
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 5
ER -