CCL1

What is ccl1 protein?

CCL1, also known as chemokine (C-C motif) ligand 1, is a small cytokine belonging to the CC chemokine family that was previously called I-309. It is produced by activated T cells and has been identified as a potent chemoattractant for monocytes, T lymphocytes, and eosinophils. The chemokine CCL1 is also involved in immunoregulatory and inflammatory processes.

The discovery of CCL1 protein dates back to the earlier years of chemokine research in the 1990s. This small protein of about 8-14 kDa was initially termed I-309 due to its immune cell activity. The protein was re-designated later on as CCL1 under a systematic nomenclature following chemokine characterizations.

CCL1 protein consists of 74 amino acids, with four cysteine residues involved in the formation of two disulfide bonds that connect Cys11 to Cys50 and Cys12 to Cys34. The structure of the monomeric chemokine accommodates an extended N-terminus, a three-stranded beta sheet, and a C-terminal alpha helix, which are commonly found in most members of the chemokine family.

The structural consensus of CCL1 is juxtaposed by its unique receptor specificity. Among the 19 human CC chemokines, CCL1 is the only one that binds the receptor CCR8 selectively. This specific relationship between ligand and receptor prevents the interaction with other cell types expressing alternative receptors, making CCL1 signaling more precise and narrow in scope compared to many other chemokine signals.

CCL1 protein plays a significant role in T cell activation and inflammatory processes. Its abnormal signaling has been implicated in various pathologies like allergies, autoimmunity, and cancer, and it's often seen as a potential therapeutic target.

What is the function of ccl1 protein?

Chemoattraction - It acts as a chemoattractant for immune cells like T lymphocytes, monocytes, dendritic cells and eosinophils by binding to the CCR8 receptor.

Cell recruitment - CCL1 recruits these leukocytes to sites of inflammation, infection or injury by inducing directed migration/chemotaxis.

T cell trafficking - It plays an important role in trafficking T lymphocytes to lymph nodes and sites of antigen presentation.

Inflammation - CCL1 contributes to inflammatory responses by stimulating migration and infiltration of immune cells into tissues.

CCL1 related signaling pathway

CCR8 signaling pathway: Binding of CCL1 to its receptor CCR8 on immune cells activates downstream G-protein coupled signaling cascades.

JAK-STAT signaling pathway: CCL1 stimulation leads to phosphorylation of JAK kinases and STAT proteins, regulating gene expression of pro-inflammatory cytokines.

MAPK signaling pathway: CCL1 activates MAPKs like ERK, JNK and p38 kinases involved in cell migration, proliferation and inflammatory responses.

NF-κB signaling pathway: CCL1 stimulation activates NF-κB, a major pro-inflammatory transcription factor inducing chemokines and adhesion molecules.

CCL1 Related Diseases

Cancer: Upregulated in several cancers like breast, prostate and lung cancers. Promotes proliferation and metastasis via leukocyte recruitment.

Asthma: Increased levels in asthmatic airways contribute to eosinophilic inflammation.

Autoimmune diseases: Higher CCL1 levels seen in multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease.

Atopic dermatitis: Plays a role in allergic skin inflammation by recruiting T cells and eosinophils.

Biomedical Application of CCL1 Protein

Cancer immunotherapy: CCL1 inhibitors may block tumor-promoting inflammation and metastasis.

Anti-angiogenic therapy: Targeting CCL1's pro-angiogenic role offers new avenues to cut off blood supply to tumors.

Anti-inflammatory drug development: Agents modulating CCL1 signaling could help treat inflammatory/autoimmune conditions.