1. Signaling Pathways
  2. GPCR/G Protein
  3. Class B GPCR

Class B GPCR

Synonyms: Secretin Family

Class B GPCRs are divided into two subfamilies: secretin (B1) and adhesion (B2). Secretin subfamily members are characteristic of large extracellular domains (ECDs) and bind to vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating peptide (PACAP), corticotropin-releasing factor (CRF), parathyroid peptide hormone (PTH), growth hormone-releasing hormone (GHRH), calcitonin gene-related peptide (CGRP), glucagon, and glucagon-like peptides (GLPs), respectively. The ligands for receptors in this secretin family are polypeptide hormones of 27-141 amino acid residues. Adhesion subfamily possesses unique N-terminal motifs, such as epidermal growth factor, cadherin, and immunoglobulin domains. They are distinguished from other GPCRs due to their roles in cell adhesion and migration. Apart from the long N-terminal domain, other unique features of the adhesion subfamily are the GPCR autoproteolysis-inducing domain and the proteolysis site that are responsible for signaling activation through a Stachel sequence (a tethered agonist) and producing N-terminal fragment (NTF) and C-terminal fragment. The hallmarks of the adhesion GPCR subfamily are a two-step activation model, the ligand–NTF interaction and the Stachel signaling/basal activity. In this class, receptors of glucagon family peptides, followed by CGRP, PTH, GHRH, CRF, VIP, and PACAP, constitute major targets for therapeutic intervention of various diseases, including obesity, T2DM, osteoporosis, migraine, depression, and anxiety.