GROWTH-HORMONE RECEPTOR BINDING PROTEIN - PHYSIOLOGY AND FUNCTION/

Soluble truncated forms of the growth hormone receptor (GHR) are prese nt in the circulation of many species and are also produced by many ti ssues/cell types. The major high-affinity forms of these GH-binding pr oteins (GHBP) are derived by alternative splicing of GHR mRNA in roden ts, but probably by proteolytic cleavage in other species. Questions s till remain with respect to the origins, native molecular form(s), phy siology, and function of the GHBPs, however. The observation that GH i nduces dimerization of the soluble GHBP and membrane GHR, and that dim erization of GHR appears to be critical for GH bioactivity suggests th at the presentation of GH to target cells, in an unbound form or as a monomeric or dimeric complex with GHBP, may have significant implicati ons for the ability of GH to activate specific postreceptor signalling pathways (tyrosine kinase, protein kinase C, G-protein pathways) know n to be utilized by GH for its diverse biological effects. This minire view addresses some of these aspects and highlights several new questi ons which have arisen as a result of recent advances in our understand ing of the structure, function, and signaling mechanisms of the membra ne bound GHR.