Introduction of CCR-6

CCR-6, also known as cluster of differentiation 196 (CD196), CKR-L3 or GPR-CY4, is a membrane receptor protein that belongs to family A of G protein-coupled receptor superfamily. It is encoded by CCR6 gene and acts as a receptor for the C-C type chemokine (CCL20), which is alternatively called macrophage inflammatory protein 3 alpha (MIP-3 alpha) or liver activation-regulated chemokine (LARC), and subsequently transduces a signal by up-regulating the intracellular calcium ion levels. It is mainly expressed in lymphocytes, T-cells, and B-cells.

Function of CCR-6 Membrane Protein

Chemokines and their receptors are crucial for the transportation of immune cells. The regulation of chemokines and their receptors contribute to both immune system homeostasis and inflammation. The CCL20-CCR6 pair contributes to the chemotaxis of dendritic cells (DC), effector / memory T-cells and B-cells, and also plays a crucial role at skin and mucosal surfaces under homeostatic and inflammatory conditions, as well as in pathologies, such as cancer and various autoimmune diseases. A meta-analysis study has indicated that CCR-6 is significantly associated with in all racial groups except African-American subgroup. CCR6-mediated signals are pivotal for immune responses to microbes in the intestinal mucosa and in the modulation of inflammatory responses initiated by tissue insult and trauma. Additionally, this receptor could positively regulate sperm motility and chemotaxis through binding with CCL20.

Application of CCR-6 Membrane Protein in Literature

1. Diao R., et al. In vitro chemokine (C-C motif) receptor 6-dependent non-inflammatory chemotaxis during spermatogenesis. Biol Res. 2018, 51(1): 12. PubMed ID: 29788995

This article focused on the expression and functional significance of CCR6 in the process of spermatogenesis and indicated that CCR6 is involved in the chemotaxis of spermatogenic cells in vitro and promotes chemotaxis under non-inflammatory conditions during normal spermatogenesis.

2. Lu M.Y., et al. The Phosphorylation of CCR6 on Distinct Ser/Thr Residues in the Carboxyl Terminus Differentially Regulates Biological Function. Front Immunol. 2018, 9: 415. PubMed ID: 29552015

This article reveals that ligand binding to CCR6 induces receptor phosphorylation at Ser/Thr residues in the C-terminal tail, rather than intracellular loops and the effects of site-specific Ser/Thr phosphorylation on CCR6 demonstrate the existence of barcodes on the protein that dictate the activation of different cell signaling profiles and lead to distinct biological outcomes.

3. Liu J., et al. Expression of CCR6 in esophageal squamous cell carcinoma and its effects on epithelial-to-mesenchymal transition. Oncotarget. 2017, 8(70): 115244-115253. PubMed ID: 29383156

Authors in this group detected the expression of C-C motif chemokine receptor 6 (CCR6) and epithelial-to-mesenchymal transition (EMT) markers in esophageal tissues/cells and evaluated the effects of CCR6 on ESCC cells proliferation, migration, and invasion in response to C-C motif chemokine ligand 20 (CCL20) treatment.

4. Doucet M., et al. CCL20/CCR6 Signaling Regulates Bone Mass Accrual in Mice. J Bone Miner Res. 2016, 31(7): 1381-90. PubMed ID: 26890063

This article focuses on the role of CCL20/CCR6 signaling in regulating bone mass and demonstrated that CCL20/CCR6 signaling may play an important role in regulating bone mass accrual, potentially by modulating osteoblast maturation, survival, and the recruitment of osteoblast-supporting cells.

5. Nandi B., et al. Stromal CCR6 drives tumor growth in a murine transplantable colon cancer through recruitment of tumor-promoting macrophages. Oncoimmunology. 2016, 5(8): e1189052. PubMed ID: 27622061

This article evaluates the correlation of CCR6 expression and colon cancer, and support the exploration of targeting the CCL20-CCR6 pathway for the treatment of colon cancer.

CCR-6 Preparation Options

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