RECEPTOR RECOGNITION BY HISTIDINE 16 OF HUMAN EPIDERMAL GROWTH-FACTORVIA HYDROGEN-BOND DONOR ACCEPTOR INTERACTIONS/

Citation
K. Nandagopal et al., RECEPTOR RECOGNITION BY HISTIDINE 16 OF HUMAN EPIDERMAL GROWTH-FACTORVIA HYDROGEN-BOND DONOR ACCEPTOR INTERACTIONS/, Journal of cellular biochemistry, 72(1), 1999, pp. 16-24
Citations number
49
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biology,"Cell Biology
ISSN journal
0730-2312
Volume
72
Issue
1
Year of publication
1999
Pages
16 - 24
Database
ISI
SICI code
0730-2312(1999)72:1<16:RRBH1O>2.0.ZU;2-9
Abstract
Human epidermal growth factor (hEGF) and human transforming growth fac tor alpha (hTGF alpha) are prototypical of structurally related polype ptide mitogens which interact with the epidermal growth factor recepto r (EGFR). Several determinants of receptor recognition that specify fu nction have been proposed on the basis of structural criteria. This st udy evaluates the role of one such candidate, H16 of hEGF, by site-spe cific mutagenesis. When assayed for receptor tyrosine kinase stimulati on using (Glu(4),Tyr(1))(n) as the exogenous substrate in vitro, the r elative agonist activities of position 16 mutants range from 14-263% o f wild-type hEGF. The rank order of potency was round to correlate wit h the relative receptor binding affinities of the mutants, which range from 7-272% of wild-type, as determined by radioreceptor competition assays. The mitogenic activity of the H16 mutants is similar to that o f wild-type hEGF as determined by clonogenic assays using rat tracheal epithelial cells. While the colony forming efficiencies do not reflec t significant differences in growth rate or survival characteristics i n the presence of the hEGF variants, it is reduced to 1.6% in control cultures which lack EGF in the medium. The results show that H16 of hE GF, although not essential for mitogenic activity, optimizes receptor recognition by hydrogen-bond donor/acceptor interactions and may share this feature with H18 of hTGF alpha. J. Cell. Biochem, 72:16-24, 1999 . (C) 1998 Wiley-Liss, Inc.