GPR1
GPR1 (also designated chemerin receptor 2, CMKLR2) is a class A G protein-coupled receptor that functions as an endogenous receptor for the adipokine and chemoattractant protein chemerin, extending the biological activity of the chemerin signaling system beyond CMKLR1-mediated responses[1][2]. Mechanistically, chemerin binding to GPR1 promotes β-arrestin recruitment, receptor internalization, and limited calcium mobilization, indicating that GPR1 primarily regulates chemerin availability and downstream signaling dynamics rather than eliciting strong canonical G protein activation[2]. This receptor participates in metabolic and inflammatory regulation, and genetic studies in knockout mice suggest a role for GPR1 in glucose homeostasis during obesity-associated metabolic dysfunction[1][3]. In disease-relevant models, GPR1 expression has been detected together with chemerin signaling components in reproductive tissues and several tumor systems, supporting investigation of the receptor in endocrine, metabolic, and cancer-related pathways[4][5]. Compared with related chemerin-binding receptors, CMKLR1 functions as a robust signaling receptor, whereas CCRL2 mainly binds and presents chemerin without productive signal transduction; therefore, GPR1 occupies an intermediate and functionally distinct position within the chemerin receptor network[4][6][7]. For experimental applications, GPR1 is frequently studied through chemerin-dependent β-arrestin assays, receptor trafficking analyses, and comparative receptor-signaling models designed to distinguish receptor-specific effects within the chemerin system[2].
References:
- [1]. Kennedy AJ, et al. International Union of Basic and Clinical Pharmacology CIII: Chemerin Receptors CMKLR1 (Chemerin1) and GPR1 (Chemerin2) Nomenclature, Pharmacology, and Function. Pharmacol Rev. 2018 Jan;70(1):174-196. [Content Brief]
- [2]. De Henau O, et al. Signaling Properties of Chemerin Receptors CMKLR1, GPR1 and CCRL2. PLoS One. 2016 Oct 7;11(10):e0164179. [Content Brief]
- [3]. Kennedy AJ, et al. International Union of Basic and Clinical Pharmacology CIII: Chemerin Receptors CMKLR1 (Chemerin1) and GPR1 (Chemerin2) Nomenclature, Pharmacology, and Function. Pharmacol Rev. 2018 Jan;70(1):174-196. [Content Brief]
- [4]. Gudelska M, et al. The expression of chemerin and its receptors (CMKLR1, GPR1, CCRL2) in the porcine uterus during the oestrous cycle and early pregnancy and in trophoblasts and conceptuses. Animal. 2020 Oct;14(10):2116-2128. [Content Brief]
- [5]. Shin WJ, et al. Mechanisms and Functions of Chemerin in Cancer: Potential Roles in Therapeutic Intervention. Front Immunol. 2018 Nov 30;9:2772. [Content Brief]
- [6]. Yoshimura T, et al. Chemokine-like receptor 1 (CMKLR1) and chemokine (C-C motif) receptor-like 2 (CCRL2); two multifunctional receptors with unusual properties. Exp Cell Res. 2011 Mar 10;317(5):674-84. [Content Brief]
- [7]. Kisielewska K, et al. Expression of chemerin receptors CMKLR1, GPR1 and CCRL2 in the porcine pituitary during the oestrous cycle and early pregnancy and the effect of chemerin on MAPK/Erk1/2, Akt and AMPK signalling pathways. Theriogenology. 2020 Nov;157:181-198. [Content Brief]
