Alteration in the Receptor Binding Specificity of Human Growth Hormone by Genomic Exon Exchange

The biological activities of the GH-PRL family of hormones are mediated by selective binding to two classes of cell membrane receptors, somatogen and lactogen. Primate GH such as human GH (hGH) are unusual in that they bind to both classes of receptors. Replacement of exons 3 or 4 of the hGH gene by the corresponding exons of the rat PRL or rat GH genes results in the synthesis of chimeric proteins which retain the ability to bind to lactogen receptors but can no longer bind to somatogen receptors. This selective loss of somatogen receptor binding in the chimeric proteins suggests that certain of the structural determinants of somatogen and lactogen receptor binding activities in hGH are distinct and can be separately modified by a limited number of amino acid substitutions.