Pathways & interactions
CC chemokine receptor 2 (IPR002237)
Short name: Chemokine_CCR2
Chemokines (chemotactic cytokines) are a family of chemoattractant molecules. They attract leukocytes to areas of inflammation and lesions, and play a key role in leukocyte activation. Originally defined as host defense proteins, chemokines are now known to play a much broader biological role [PMID: 11544102]. They have a wide range of effects in many different cell types beyond the immune system, including, for example, various cells of the central nervous system [PMID: 9689100], and endothelial cells, where they may act as either angiogenic or angiostatic factors [PMID: 7592998].
The chemokine family is divided into four classes based on the number and spacing of their conserved cysteines: 2 Cys residues may be adjacent (the CC family); separated by an intervening residue (the CXC family); have only one of the first two Cys residues (C chemokines); or contain both cysteines, separated by three intervening residues (CX3C chemokines).
Chemokines exert their effects by binding to rhodopsin-like G protein-coupled receptors on the surface of cells. Following interaction with their specific chemokine ligands, chemokine receptors trigger a flux in intracellular calcium ions, which cause a cellular response, including the onset of chemotaxis. There are over fifty distinct chemokines and least 18 human chemokine receptors [PMID: 10714678]. Although the receptors bind only a single class of chemokines, they often bind several members of the same class with high affinity. Chemokine receptors are preferentially expressed on important functional subsets of dendritic cells, monocytes and lymphocytes, including Langerhans cells and T helper cells [PMID: 10601351, PMID: 9500790]. Chemokines and their receptors can also be subclassified into homeostatic leukocyte homing molecules (CXCR4, CXCR5, CCR7, CCR9) versus inflammatory/inducible molecules (CXCR1, CXCR2, CXCR3, CCR1-6, CX3CR1).
CC chemokine receptors are a subfamily of the chemokine receptors that specifically bind and respond to cytokines of the CC chemokine family. There are currently ten members of the CC chemokine receptor subfamily, named CCR1 to 10. The receptors receptors are found in monocytes, lymphocytes, basophils and eosinophils.
This entry represents CC chemokine receptor 2 (CCR2), it is a receptor for the monocyte chemoattractant protein-1 (CCL2), a chemokine which specifically mediates monocyte chemotaxisis involved in monocyte infiltration in inflammatory diseases such as rheumatoid arthritis [PMID: 14674010] as well as in the inflammatory response against tumors [PMID: 16215992]. It has also been shown that CCR2 deficient mice develop an accelerated Alzheimer's-like pathology in comparison to wild type mice [PMID: 17351623, PMID: 20136653, PMID: 22607625]. CCR2 has also been shown to function in blood vessel remodeling [PMID: 17479183]. Following interaction with specific CC chemokine ligands, CCR2 triggers a flux in intracellular calcium ions [PMID: 8146186, PMID: 9514408] and inhibition of adenylyl cyclase [PMID: 10587439]. This causes cell responses, including the recruitment of mononuclear phagocytes into the CNS, leading to chemotaxis [PMID: 10587439].
GO:0007186 G-protein coupled receptor signaling pathway
GO:0001974 blood vessel remodeling
GO:0006955 immune response
GO:0006954 inflammatory response
GO:0090026 positive regulation of monocyte chemotaxis
GO:0016493 C-C chemokine receptor activity
GO:0016021 integral component of membrane
- PR01107 (CHEMOKINER2)