Barbacci E G, Guarino B C, Stroh J G, Singleton D H, Rosnack K J, Moyer J D, Andrews G C
Pfizer Central Research, Groton, Connecticut 06340, USA.
J Biol Chem. 1995 Apr 21;270(16):9585-9. doi: 10.1074/jbc.270.16.9585.
Heregulin is a ligand for the erbB3 and erbB4 receptors, with a region of high homology to epidermal growth factor (EGF). Despite this homology, these ligands bind to their corresponding receptors with great specificity. We report here the synthesis of heregulin beta 177-241 and show that a region consisting of amino acids 177-226 is sufficient both for binding and stimulation of receptor phosphorylation. Studies of chimeric EGF/heregulin peptides revealed that amino acids 177-181 of heregulin provide the specificity for binding to the heregulin receptor. The substitution of amino acids 177-181 of heregulin for the N terminus of EGF produced a unique bifunctional agonist that binds with high affinity to both the EGF receptor and the heregulin receptor.
Heregulin是erbB3和erbB4受体的配体，与表皮生长因子（EGF）具有高度同源区域。尽管存在这种同源性，但这些配体以高度特异性结合其相应受体。我们在此报告了Heregulinβ177 - 241的合成，并表明由氨基酸177 - 226组成的区域对于结合和刺激受体磷酸化都是足够的。嵌合EGF / Heregulin肽的研究表明，Heregulin的氨基酸177 - 181提供了与Heregulin受体结合的特异性。将Heregulin的氨基酸177 - 181替换为EGF的N末端产生了一种独特的双功能激动剂，它与EGF受体和Heregulin受体都具有高亲和力结合。
