Alain B. Schreiber

A synthetic fragment of rat transforming growth factor α with receptor binding and antigenic properties

A fragment of rat transforming growth factor alpha (TGF alpha) comprising the third disulfide loop (residues 34-43) was selected as a potential antigenic and receptor binding region. Immunization of rabbits with a peptide conjugate resulted in antibodies which were specific for both the peptide and rat TGF alpha, but not for the homologous epidermal growth factor (EGF). The synthetic decapeptide exhibited low affinity for EGF receptors on human cells. Affinity was increased 100x to 0.2% of EGF or TGF alpha binding by blocking the peptide ends. The blocked decapeptide had no mitogenic activity but prevented the mitogenic effect of EGF and TGF alpha on fibroblasts. This decapeptide is an antagonist and contains an important receptor binding region of TGF alpha.

A non-mitogenic analogue of epidermal growth factor enhances the phosphorylation of endogenous membrane proteins.

Abstract The cyanogen bromide cleaved analogue of Epidermal Growth Factor (EGF) binds to EGF receptors with reduced affinity but fails to induce DNA synthesis. However, at similar receptor occupancy, cyanogen bromide cleaved EGF is as potent as EGF in enhancing the phosphorylation of endogenous membrane proteins mediated by the EGF specific, cyclic nucleotide independent protein kinase. Two possibilities arise concerning the biological role of the EGF induced membrane protein phosphorylation: 1) it is not related to the triggering of DNA synthesis by EGF and does not serve as “second messenger” for the growth factor. 2) it is a necessary but not sufficient biochemical signal for the activation of DNA synthesis by EGF.

Growth Hormone-Releasing Factor Analogues with Increased Receptor Affinity

After several erroneous earlier reports, the primary sequences of a family of related proteins exhibiting growth hormone-releasing factor (GRF) properties were reported (Guillemin et al., 1982; Rivier et al., 1982). The proteins were isolated from two different human pancreatic tumors that produced clinical signs of acromegaly, and these sequences differed only in chain length [37 (Esch et al., 1983), 40 (River et al., 1982; Esch et al, 1983), or 44 (Esch et al., 1983) residues]. Further studies with cloned human cDNA (Gubler et al., 1983; Mayo et al., 1983) or protein isolated from human hypothalami (Bohlen et al., 1983; Ling et al., 1984) suggest that the hypothalamic form of hGRF corresponds to the sequence (most likely the GRF1-44-NH2) isolated from the pancreatic tumors (Guillemin et al., 1982). The shorter sequences may result from proteolysis. More recently, the sequences of GRFs (Fig. 1) were reported from the rat (Spiess et al., 1983) and several domestic species (Brazeau et al., 1984).