Signal Protein-Derived Peptides as Functional Probes and Regulators of Intracellular Signaling

Abstract

The functionally important regions of signal proteins participating in their specific interaction and responsible for transduction of hormonal signal into cell are rather short in length, having, as a rule, 8 to 20 amino acid residues. Synthetic peptides corresponding to these regions are able to mimic the activated form of full-size signal protein and to trigger signaling cascades in the absence of hormonal stimulus. They modulate protein-protein interaction and influence the activity of signal proteins followed by changes in their regulatory and catalytic sites. The present review is devoted to the achievements and perspectives of the study of signal protein-derived peptides and to their application as selective and effective regulators of hormonal signaling systems in vitro and in vivo. Attention is focused on the structure, biological activity, and molecular mechanisms of action of peptides, derivatives of the receptors, G protein α subunits, and the enzymes generating second messengers.

The Functional State of Hormone-Sensitive Adenylyl Cyclase Signaling System in Diabetes Mellitus

“…Their action being receptor and site specific, they can induce either inhibition or enhancement of signal transduction via the cognate receptor. This is in good agreement with the results obtained with synthetic peptides derived from the extracellular and intracellular regions of different GPCRs [61, 62]. Thus, peptides corresponding to the extracellular loops of MCRs are a promising tool in the study of etiology of DM and its cerebral complications and give a perspective approach to develop new models of DM and obesity based on antibody-induced deregulation of the brain AC signaling.…”

Role of iso-receptors in receptor-receptor interactions with a focus on dopamine iso-receptor complexes

“…These include ICL 2 between TM3 and TM4, ICL 3 between TM 5 and TM 6, and loop 4 formed between TM 7 and the lipid modification on the proximal carboxyl terminus (Bockaert et al, 2004;Shpakov, 2011). Agonist binding causes steric changes in the arrangement of the TM domains that are allosterically transmitted to the associated G-protein heterotrimer (G αβγ ) that dissociate into Gα and Gβγ subunits.…”

Inhibition of the Ethanol-induced Potentiation of α1 Glycine Receptor by a Small Peptide That Interferes with Gβγ Binding

“…G protein-regulated pathways are recognized as one of the most important in terms of hormonal cell signaling mechanisms (14), and the pharmacological modification of these pathways has been a central focus of research. In this context, the use of small peptides to induce molecular interference of protein-protein interactions has been of importance in the study of molecular events in signal transduction pathways (15). However, not much is known regarding a potential pharmaco-logical modulation of ion channels and ethanol modulation using small peptides (20).…”