AROMATICITY AT POSITION-37 IN HUMAN EPIDERMAL GROWTH-FACTOR IS NOT OBLIGATORY FOR ACTIVITY

作者：ENGLER DA; HAUSER MR; COOK JS; NIYOGI SK

来源：Molecular and Cellular Biology, 1991, 11(5): 2425-2431.

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 [I-125]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 > His > Ser > Ala > Asp > Arg > Gly in both assays. All were effective, with no or only moderate reduction in potency, in stimulating the incorporation of [H-3]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 biolgoical activity.

• 出版日期1991-5