Mechanisms & Targets

signaling-pathway

AMPK signaling

A serine/threonine kinase complex that senses low cellular ATP and phosphorylates substrates that increase ATP generation and decrease ATP consumption. Reported as a central mediator of the cellular response to energetic stress and of multiple aspects of mitochondrial homeostasis.

AMP-activated protein kinase · AMPK pathway

receptor

Amylin and calcitonin receptors

The calcitonin receptor, and the amylin receptor complexes it forms when associated with receptor activity-modifying proteins RAMP1, RAMP2 or RAMP3. Because the amylin receptors are heteromers rather than distinct gene products, receptor construct and accessory-protein expression must accompany any selectivity claim; a potency ranking is not transferable between assay systems.

CALCR · CTR · AMY1 · AMY2 · AMY3 · RAMP1 · RAMP2 · RAMP3

receptor

Angiotensin receptors

The angiotensin receptor family includes the AT1 and AT2 G-protein-coupled receptors. Direct binding experiments and structures of receptor–peptide complexes establish interaction with the Ile5 angiotensin II parent. Receptor subtype, organism and engineered receptor construct are distinguished in the cited studies.

receptor

Bradykinin B2 receptor

The human bradykinin B2 receptor is a G protein-coupled receptor. The cited studies characterize bradykinin-bound receptor structures and icatibant recognition in identified receptor preparations.

receptor

CD36 scavenger receptor

A multifunctional scavenger receptor, distinct from the growth hormone secretagogue receptor, reported as a binding target for certain synthetic secretagogue peptides. It is recorded separately here precisely because collapsing it into the ghrelin-receptor mechanism would erase the finding that these compounds are not pharmacologically interchangeable.

CD36 · FAT · SR-B2

receptor

Cholecystokinin 1 receptor

The cholecystokinin 1 receptor is a class A G-protein-coupled receptor. Independent structural studies identify sulfated CCK-8 bound to this receptor.

CCK1R · CCK-A receptor · CCKAR

receptor

Corticotropin-releasing factor receptor 1

CRFR1 is a class B G-protein-coupled receptor. Independent receptor-expression and receptor-complex studies identify binding of the human/rat-sequence corticotropin-releasing factor peptide.

CRFR1

binding-interaction

Cu(II) coordination

Formation of a discrete coordination complex between a peptide ligand and a Cu(II) ion. Spectroscopic study of the glycyl-L-histidyl-L-lysine complex reports a mononuclear 1:1 species at neutral pH with equatorial nitrogen coordination including the histidyl imidazole. Complex formation changes the molecular formula, mass, and analytical identity of the species relative to the free peptide, and is reversible by competing chelators.

Copper(II) chelation · Copper-peptide complex formation

signaling-pathway

Focal adhesion kinase signaling

A cytoskeletal signaling pathway in which focal adhesion kinase and paxillin phosphorylation coordinate cell adhesion, spreading, and migration.

FAK-paxillin pathway · FAK signaling

binding-interaction

G-actin sequestration

Binding of monomeric globular actin by a peptide ligand, holding it in a form unavailable for filament assembly. Beta-thymosins are reported as the main intracellular G-actin-sequestering peptides in most vertebrate cells, with a dissociation constant in the micromolar range that permits rapid binding and release.

Actin monomer binding · G-actin binding

receptor

Galanin receptors

The galanin receptor family comprises three G protein-coupled receptors. GALR1 and GALR3 signal through Gi/o, while GALR2 signals mainly through Gq/11. Spexin activates GALR2 and GALR3 but not GALR1 in the reported ligand panel. Structural studies compared galanin-bound GALR1-Go and GALR2-Gq with spexin-bound GALR2-Gq, providing evidence for ligand recognition and subtype-dependent coupling.

GALR1 · GALR2 · GALR3 · GalR

receptor

GHRH receptor

A class B G-protein-coupled receptor expressed on anterior pituitary somatotrophs. Synthetic growth hormone-releasing factor analogs are characterized by their activity at this receptor.

GHRHR · Growth hormone-releasing hormone receptor

receptor

Glucagon receptor

GCGR is a class B G-protein-coupled receptor. Retatrutide's LY3437943 discovery record characterizes a molecular agonist relationship at GCGR alongside GIPR and GLP-1R.

GCGR

receptor

Glucagon-like peptide-1 receptor

GLP-1R is a class B G-protein-coupled receptor. The cited structural and pharmacology records characterize semaglutide and retatrutide as peptide agonists at this receptor.

GLP-1R

receptor

Glucose-dependent insulinotropic polypeptide receptor

GIPR is a class B G-protein-coupled receptor. The cited discovery and trial records identify it as one of the three receptor relationships declared for retatrutide.

GIPR

receptor

GnRH receptor

The GnRH receptor is a G-protein-coupled receptor encoded in humans by GNRHR. The records linked here cite direct binding measurements for synthetic peptide analogs, made at the human receptor or, where stated, at the rat receptor expressed in cultured cells.

GNRHR · GnRH-R

receptor

Growth hormone secretagogue receptor

A G-protein-coupled receptor distinct from the GHRH receptor. Antagonist profiling reported that ipamorelin releases growth hormone through a GHRP-like receptor rather than through the GHRH receptor, establishing the two pathways as separate.

GHS-R1a · Ghrelin receptor · GHSR

receptor

Guanylate cyclase C receptor

Guanylate cyclase C is a receptor also designated GC-C. The cited studies characterize linaclotide in membrane-binding assays and evaluate peptide activity at this receptor.

GC-C · GC-2C

receptor

Innate repair receptor

A heteromeric receptor complex proposed in 2004 to comprise the erythropoietin receptor together with the beta common receptor (CD131), and described as distinct from the EPOR homodimer that mediates erythroid maturation. The proposal rests on co-purification and co-immunoprecipitation of the two receptors from tissue membranes, colocalization in protected cells, and the absence of erythropoietin's protective activity in beta common receptor knockout animals. It is disputed. An independent group examined the extracellular regions of the two receptors in silico and in vitro, in the presence and in the absence of erythropoietin or the erythropoietin-derived peptide cibinetide, reported that they do not specifically associate, and opens by calling the complex controversial. No biophysical demonstration of a direct association between the two receptors has been published. This record therefore describes a reported complex together with the test that failed to confirm it, not an established one. Peptides characterized as selective agonists at this complex are reported not to engage the homodimeric receptor.

IRR · EPOR/CD131 heteromer · beta common receptor complex

receptor

Integrin αIIbβ3

A heterodimeric integrin whose interaction with eptifibatide is characterized by direct structural and solution studies.

GPIIb/IIIa

receptor

Kisspeptin receptor

KISS1R is a G-protein-coupled receptor historically reported as GPR54 and AXOR12. Foundational records identify KISS1-derived peptides as its endogenous ligands.

KISS1R · GPR54 · AXOR12

receptor

Melanocortin receptors

A family of five G protein-coupled receptors, MC1R through MC5R. ACTH recognition and signaling at MC2R depend on the accessory protein MRAP. Native hormones, peptide analogs and nonpeptide ligands differ in receptor-subtype recognition and functional direction; binding affinity, agonism and antagonism must be interpreted separately in the experimental system studied.

MC1R · MC2R · MC3R · MC4R · MC5R · MCR

receptor

Opioid receptors

Receptor sites characterized by direct opioid-ligand binding experiments. Historical peptide studies establish receptor binding without necessarily resolving a modern receptor subtype.

receptor

PACAP and VIP receptors

Receptor relationships involving PAC1, VPAC1 and VPAC2, with each ligand’s tested receptor subtype identified separately.

PAC1 · VPAC1 · VPAC2

receptor

Parathyroid hormone 1 receptor

PTH1R is a class B G-protein-coupled receptor encoded by PTH1R and also called the PTH/PTHrP receptor. The record linked here cites a direct binding measurement made at the human receptor expressed in a human kidney cell line.

PTH1R · PTH/PTHrP receptor

receptor

Secretin receptor

The secretin receptor, encoded by SCTR, is a class B G-protein-coupled receptor. Independent structural studies characterize human secretin bound to this receptor.

receptor

Thyrotropin-releasing hormone receptor

A class A G-protein-coupled receptor. Independent structural studies report the defined TRH tripeptide bound to human TRHR in receptor–G-protein complexes.