Growth hormone and its receptor: from structure to function

The past few years have seen a dramatic increase in knowledge in relation to the molecular structures of both growth hormone(s) (GH) and their polypeptide receptors (GHR). In addition to older data providing the sequences of numerous mammalian and nonmammalian GHs, cDNAs for mouse (Smith et al. 1989), rat (Mathews et al. 1989), rabbit, human (Leung et al. 1987), ovine (Adams et al. 1990), bovine (Hauser et al. 1990) and porcine (Cioffi et al. 1990) GHRs have recently been cloned and sequenced. Further to this, a high resolution X-ray crystal structure for porcine GH has been published (AbdelMeguid et al. 1987), and very recently the cocrystallization of human (h) GH with the extracellular domain of the GHR has been achieved (De Vos et al. 1992). These studies have revealed GHs to be 4α helix bundle proteins with one molecule of GH binding in an asymmetric fashion to two molecules of