scholarly journals Tyrosine kinase activity of the EGF receptor in murine metanephric organ culture

1995 ◽  
Vol 47 (3) ◽  
pp. 774-781 ◽  
Author(s):  
Judith L. Pugh ◽  
William E. Sweeney ◽  
Ellis D. Avner
Keyword(s):  
Organ Culture ◽  
Tyrosine Kinase ◽  
Kinase Activity ◽  
Egf Receptor ◽  
Tyrosine Kinase Activity

scholarly journals Rapid uptake of tyrphostin into A431 human epidermoid cells is followed by delayed inhibition of epidermal growth factor (EGF)-stimulated EGF receptor tyrosine kinase activity.

1991 ◽  
Vol 11 (5) ◽  
pp. 2697-2703 ◽  
Author(s):  
C A Faaland ◽  
F H Mermelstein ◽  
J Hayashi ◽  
J D Laskin
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Kinase Activity ◽  
Egf Receptor ◽  
Tyrosine Kinase Activity ◽  
A431 Cells ◽  
Epidermal Growth

Treatment of A431 human epidermoid cells with epidermal growth factor (EGF; 20 nM) results in decreased proliferation. This is associated with blockage of the cells in the S and/or G2 phases of the cell cycle. We found that tyrphostin, a putative tyrosine kinase inhibitor, in the range of 50 to 100 microM, partially reversed the growth-inhibitory and cell cycle changes induced by EGF. By using high-pressure liquid chromatography with electrochemical detection, we found that tyrphostin was readily incorporated into A431 cells, reaching maximal levels within 1 h. Although tyrphostin (50 to 100 microM) had no effect on high-affinity binding of EGF to its receptor in A431 cells for up to 24 h, the compound partially inhibited EGF-stimulated EGF receptor tyrosine kinase activity. However, this effect was evident only after prolonged treatment of the cells (4 to 24 h) with the drug. When the peak intracellular concentration of tyrphostin occurred (1 h), no inhibition of tyrosine kinase activity was observed. After both 1 and 24 h, tyrphostin was a less effective inhibitor of tyrosine kinase activity than the potent tumor promoter 12-O-tetradecanoyl phorbol-13-acetate, which almost completely blocked EGF receptor autophosphorylation. On the basis of our data, we hypothesize that tyrphostin is not a competitive inhibitor of the EGF receptor tyrosine kinase in intact cells and that it functions by an indirect mechanism.

scholarly journals Signal transduction by epidermal growth factor and heregulin via the kinase-deficient ErbB3 protein

1998 ◽  
Vol 334 (1) ◽  
pp. 189-195 ◽  
Author(s):  
Hong-Hee KIM ◽  
Ulka VIJAPURKAR ◽  
Nathan J. HELLYER ◽  
Dolores BRAVO ◽  
John G. KOLAND
Keyword(s):  
Signal Transduction ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Kinase Activity ◽  
Egf Receptor ◽  
Tyrosine Kinase Activity ◽  
Epidermal Growth ◽  
Protein Tyrosine Kinase Activity

The role of protein tyrosine kinase activity in ErbB3-mediated signal transduction was investigated. ErbB3 was phosphorylated in vivo in response to either heregulin (HRG) in cells expressing both ErbB3 and ErbB2, or epidermal growth factor (EGF) in cells expressing both ErbB3 and EGF receptor. A recombinant receptor protein (ErbB3-K/M, in which K/M stands for Lys → Met amino acid substitution) containing an inactivating mutation in the putative ATP-binding site was also phosphorylated in response to HRG and EGF. Both the wild-type ErbB3 and mutant ErbB3-K/M proteins transduced signals to phosphatidylinositol 3-kinase, Shc and mitogen-activated protein kinases. Separate kinase-inactivating mutations in the EGF receptor and ErbB2 proteins abolished ErbB3 phosphorylation and signal transduction activated by EGF and HRG respectively. Hence the protein tyrosine kinase activity necessary for growth factor signalling via the ErbB3 protein seems to be provided by coexpressed EGF and ErbB2 receptor proteins.

scholarly journals Inhibition of tyrosine kinase activity of the epidermal growth factor (EGF) receptor by a truncated receptor form that binds to EGF: role for interreceptor interaction in kinase regulation.

1989 ◽  
Vol 9 (2) ◽  
pp. 671-677 ◽  
Author(s):  
A Basu ◽  
M Raghunath ◽  
S Bishayee ◽  
M Das
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Binding Site ◽  
Kinase Activity ◽  
Egf Receptor ◽  
Kinase Domain ◽  
Tyrosine Kinase Activity ◽  
Truncated Receptor ◽  
Epidermal Growth

The tyrosine kinase activity of the epidermal growth factor (EGF) receptor is regulated by a truncated receptor of 100 kilodaltons (kDa) that contains the EGF-binding site but not the kinase domain. The inhibition of kinase is not due to competition for available EGF or for the kinase substrate-binding site. Chemical cross-linking studies suggest that the 100-kDa receptor may form a heterodimer with the intact EGF receptor. Structurally related receptor kinases, such as the platelet-derived growth factor receptor, the insulin receptor, and the Neu receptor, were not inhibited by the 100-kDa receptor. The results indicate that (i) the inhibition was specific for the EGF receptor, (ii) the kinase domain had little or no role in determining target specificity, and (iii) the regulation of kinase may be due to a specific interaction of the 100-kDa receptor with the ligand-binding domain of the EGF receptor kinase.

p185, a product of the neu proto-oncogene, is a receptorlike protein associated with tyrosine kinase activity

1986 ◽  
Vol 6 (5) ◽  
pp. 1729-1740
Author(s):  
D F Stern ◽  
P A Heffernan ◽  
R A Weinberg
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Kinase Activity ◽  
Egf Receptor ◽  
Growth Factor Receptor ◽  
Culture Conditions ◽  
Tyrosine Kinase Activity ◽  
Electrophoretic Mobilities ◽  
Epidermal Growth ◽  
Neu Oncogene

The neu oncogene was originally identified in cell lines derived from rat neuroectodermal tumors. neu is related to but distinct from the c-erbB gene, which encodes the epidermal growth factor (EGF) receptor. neu encodes a protein, designated p185, that is serologically related to the EGF receptor. Identification of the normal homolog of p185 encoded by the neu proto-oncogene enabled us to compare the product of the neu proto-oncogene with the mutated version specified by the neu oncogene and with the EGF receptor. The normal form of p185 was structurally similar to its transforming counterpart, indicating that activation of the neu oncogene did not cause major structural alterations in the gene product. Both normal and transforming forms of p185 were associated with tyrosine kinase activity, supporting the idea that normal p185 functions as a growth factor receptor. p185 differed both structurally and functionally from the EGF receptor. p185 and the EGF receptor had distinct electrophoretic mobilities when synthesized under normal culture conditions or in the presence of tunicamycin. EGF did not stimulate increased turnover of p185 and did not bind quantitatively to p185. A number of other growth factors failed to stimulate degradation of p185 or tyrosine phosphorylation of p185 and are therefore unlikely to be ligands for p185.

scholarly journals p185, a product of the neu proto-oncogene, is a receptorlike protein associated with tyrosine kinase activity.

1986 ◽  
Vol 6 (5) ◽  
pp. 1729-1740 ◽  
Author(s):  
D F Stern ◽  
P A Heffernan ◽  
R A Weinberg
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Kinase Activity ◽  
Egf Receptor ◽  
Growth Factor Receptor ◽  
Culture Conditions ◽  
Tyrosine Kinase Activity ◽  
Electrophoretic Mobilities ◽  
Epidermal Growth ◽  
Neu Oncogene

The neu oncogene was originally identified in cell lines derived from rat neuroectodermal tumors. neu is related to but distinct from the c-erbB gene, which encodes the epidermal growth factor (EGF) receptor. neu encodes a protein, designated p185, that is serologically related to the EGF receptor. Identification of the normal homolog of p185 encoded by the neu proto-oncogene enabled us to compare the product of the neu proto-oncogene with the mutated version specified by the neu oncogene and with the EGF receptor. The normal form of p185 was structurally similar to its transforming counterpart, indicating that activation of the neu oncogene did not cause major structural alterations in the gene product. Both normal and transforming forms of p185 were associated with tyrosine kinase activity, supporting the idea that normal p185 functions as a growth factor receptor. p185 differed both structurally and functionally from the EGF receptor. p185 and the EGF receptor had distinct electrophoretic mobilities when synthesized under normal culture conditions or in the presence of tunicamycin. EGF did not stimulate increased turnover of p185 and did not bind quantitatively to p185. A number of other growth factors failed to stimulate degradation of p185 or tyrosine phosphorylation of p185 and are therefore unlikely to be ligands for p185.

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