Analogs of human epidermal growth factor which partially inhibit the growth factor-dependent protein-tyrosine kinase activity of the epidermal growth factor receptor
- PMID: 2159890
- DOI: 10.1016/0014-5793(90)80776-f
Analogs of human epidermal growth factor which partially inhibit the growth factor-dependent protein-tyrosine kinase activity of the epidermal growth factor receptor
Abstract
Three site-directed mutants of human epidermal growth factor, Leu-26----Gly, Leu-47----Ala, and Ile-23----Thr, were examined for their ability to stimulate the protein-tyrosine kinase activity of the epidermal growth factor receptor. The receptor binding affinities of the mutant growth factors were 20- to 50-fold lower, as compared to wild-type growth factor. At saturating concentrations of growth factor, the velocities of the phosphorylation of exogenously added substrate and receptor autophosphorylation were significantly lower with the mutant analogs, suggesting a partial 'uncoupling' of signal transduction. The mutant analogs were shown to compete directly with the binding of wild-type, resulting in a decrease in growth factor-stimulated kinase activity.
Similar articles
-
Biochemical properties of site-directed mutants of human epidermal growth factor: importance of solvent-exposed hydrophobic residues of the amino-terminal domain in receptor binding.Biochemistry. 1990 Oct 23;29(42):9988-93. doi: 10.1021/bi00494a032. Biochemistry. 1990. PMID: 2271634
-
Blocking of EGF-dependent cell proliferation by EGF receptor kinase inhibitors.Science. 1988 Nov 11;242(4880):933-5. doi: 10.1126/science.3263702. Science. 1988. PMID: 3263702
-
Inhibition of tyrosine kinase activity decreases expression of surfactant protein A in a human lung adenocarcinoma cell line independent of epidermal growth factor receptor.Biochim Biophys Acta. 1997 Mar 1;1355(3):218-30. doi: 10.1016/s0167-4889(96)00134-6. Biochim Biophys Acta. 1997. PMID: 9060993
-
Signal transduction system for growth factor receptors associated with tyrosine kinase activity: epidermal growth factor receptor signalling and its regulation.Cell Signal. 1992 Mar;4(2):123-32. doi: 10.1016/0898-6568(92)90076-k. Cell Signal. 1992. PMID: 1616819 Review. No abstract available.
-
Interaction of epidermal growth factor with its receptor.Prog Nucleic Acid Res Mol Biol. 1994;49:353-83. doi: 10.1016/s0079-6603(08)60055-0. Prog Nucleic Acid Res Mol Biol. 1994. PMID: 7863010 Review. No abstract available.
Cited by
-
Ligand binding and dynamics of the monomeric epidermal growth factor receptor ectodomain.Proteins. 2013 Nov;81(11):1931-43. doi: 10.1002/prot.24339. Epub 2013 Aug 19. Proteins. 2013. PMID: 23760854 Free PMC article.
-
Structure-function studies of mEGF: probing the type I beta-turn between residues 25 and 26.J Protein Chem. 1995 Nov;14(8):753-62. doi: 10.1007/BF01886915. J Protein Chem. 1995. PMID: 8747437
-
A 34-kd protein with strong homology to ras-like proteins inhibits epidermal growth factor activity.Am J Pathol. 1993 Apr;142(4):1141-53. Am J Pathol. 1993. PMID: 8475991 Free PMC article.
-
Aromaticity at position 37 in human epidermal growth factor is not obligatory for activity.Mol Cell Biol. 1991 May;11(5):2425-31. doi: 10.1128/mcb.11.5.2425-2431.1991. Mol Cell Biol. 1991. PMID: 1850095 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
