Document Detail


Aromaticity at position 37 in human epidermal growth factor is not obligatory for activity.
MedLine Citation:
PMID:  1850095     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The third disulfide loop (amino acids 33 to 42) of human epidermal growth factor (hEGF) encompasses the region of highest amino acid conservation among all of the EGF-like family of molecules. The importance of some of these highly conserved residues for the maintenance of biological activity, especially the aromatic amino acid tyrosine at position 37, has until now been considered essential on the basis of previous studies with the EGF-like molecule transforming growth factor alpha. Variants at the Tyr-37 position of hEGF were constructed by site-directed mutagenesis. The substituting amino acids were phenylalanine, histidine, serine, alanine, aspartic acid, arginine, and glycine. The variants were tested for their ability to competitively displace native [125I]hEGF from its receptor and to stimulate the protein-tyrosine kinase activity of the receptor; the order of efficacy of substituting amino acids was Phe greater than His greater than Ser greater than Ala greater than Asp greater than Arg greater than Gly in both assays. All were effective, with no or only moderate reduction in potency, in stimulating the incorporation of [3H]thymidine into acid-insoluble material of quiescent mouse A31 cells. Only Tyr-37----Ala, Tyr-37----Arg and Tyr-37----Gly were slightly less potent in the cell assay. Thus, neither tyrosine nor another aromatic amino acid at position 37 in hEGF is essential for full biological activity.
Authors:
D A Engler; M R Hauser; J S Cook; S K Niyogi
Related Documents :
563875 - Valine, leucine, and isoleucine metabolism by lactating bovine mammary tissue.
4552845 - Microbiological assay of amino acids in serum: valine, leucine, and methionine.
699715 - Amino acid metabolism in the heart muscle in subjects with ischaemic heart disease at r...
8344335 - Tritium and 14c isotope effects using tracers of leucine and alpha-ketoisocaproate.
15279975 - Chemical constituents of leaves and stem bark of plumeria obtusa.
2745255 - Bactericidal effects of amoxycillin/clavulanic acid against legionella pneumophila.
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  11     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  1991 May 
Date Detail:
Created Date:  1991-05-21     Completed Date:  1991-05-21     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2425-31     Citation Subset:  IM    
Affiliation:
University of Tennessee-Oak Ridge Graduate School of Biomedical Sciences and the Protein Engineering and Molecular Mutagenesis, Oak Ridge National Laboratory 37831-8077.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Base Sequence
Binding, Competitive
Epidermal Growth Factor / genetics*,  metabolism,  pharmacology
Humans
Kinetics
Molecular Sequence Data
Mutagenesis, Site-Directed
Oligonucleotide Probes / chemical synthesis
Protein-Tyrosine Kinases / drug effects,  metabolism
Receptor, Epidermal Growth Factor / metabolism
Restriction Mapping
Sequence Homology, Nucleic Acid
Grant Support
ID/Acronym/Agency:
CA 50735/CA/NCI NIH HHS; T32 CA 09104/CA/NCI NIH HHS; T32 CA 09336/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Oligonucleotide Probes; 62229-50-9/Epidermal Growth Factor; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.10.1/Receptor, Epidermal Growth Factor
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Genetic evidence that different functional domains of the PET54 gene product facilitate expression o...
Next Document:  Heterodimers of myogenic helix-loop-helix regulatory factors and E12 bind a complex element governin...