Chemokine & Receptor Background

What are Chemokines
Chemokines (movement, Greek -kinos ) belong to a family of cytokines , and they are small proteins secreted by cells. The name is derived from their function to induce directed chemotaxis in nearby responsive cells; they are chemotactic cytokines. Proteins are classified as chemokines mainly when they share the common structural characteristics such as small size (they are all approximately 8-10 kilodaltons in size), and the presence of four cysteine residues in conserved locations that are key to forming their 3-dimensional shape. Learn More.

Chemokine Structure and Function
Chemokines are structurally and functionally related 8–10 kDa peptides that are the products of distinct genes clustered on human chromosomes 4 and 17 and can be found at sites of inflammation. They are approximately 20-50% identical to each other; that is, they share gene sequence and amino acid sequence homology. They all also possess conserved amino acids that are important for creating their 3-dimensional or tertiary structure, such as (in most cases) four cysteines that interact with each other in pairs to create a Greek key shape that is a characteristic of chemokines. The chemokine fold is conserved across subfamilies and is composed of a three-stranded anti-parallel beta-sheet, which is preceded by a disordered amino terminus and covered on one side by a carboxy-terminal alpha-helix. Learn More.

Chemokine Family
Chemokines are the largest family of cytokines in human immunophysiology. These proteins are defined by four invariant cysteines and are categorized based on the sequence around the first two cysteines, which leads to two major and two minor subfamilies. Learn More.

Chemokine Receptor / Chemokine Receptors
Chemokine receptors are G protein-coupled receptors containing 7 transmembrane domains that are found on the surface of leukocytes. Chemokines function by activating specific G protein–coupled receptors, which results in, among other functions, the migration of inflammatory and noninflammatory cells to the appropriate tissues or compartments within tissues. Approximately 19 different chemokine receptors have been characterized to date, which are divided into four families depending on the type of chemokine they bind; CXCR that bind CXC chemokines, CCR that bind CC chemokines, CX3CR1 that binds the sole CX3C chemokine (CX3CL1), and XCR1 that binds the two XC chemokines (XCL1 and XCL2). Learn More.

Chemokine Signaling
Chemokine receptors associate with G-proteins to transmit cell signals following ligand binding. Activation of G proteins, by chemokine receptors, causes the subsequent activation of an enzyme known as phospholipase C (PLC). PLC cleaves a molecule called phosphatidylinositol (4,5)-bisphosphate (PIP2) into two second messenger molecules known as Inositol triphosphate (IP3) and diacylglycerol (DAG) that trigger intracellular signaling events; DAG activates another enzyme called protein kinase C (PKC), and IP3 triggers the release of calcium from intracellular stores. These events promote many signaling cascades (such as the MAP kinase pathway) that generate responses like chemotaxis, degranulation, release of superoxide anions and changes in the avidity of cell adhesion molecules called integrins within the cell harbouring the chemokine receptor. Learn More.

Chemokine Inflammation
Inflammation is mediated by a variety of soluble factors, including a group of secreted polypeptides known as cytokines. Some cytokines act to make disease worse (proinflammatory cytokines), whereas others serve to reduce inflammation and promote healing (anti-inflammatory cytokines). Some chemokines are considered pro-inflammatory and can be induced during an immune response to recruit cells of the immune system to a site of infection, while others are considered homeostatic and are involved in controlling the migration of cells during normal processes of tissue maintenance or development. Inflammatory chemokines function mainly as chemoattractants for leukocytes, recruiting monocytes, neutrophils and other effector cells from the blood to sites of infection or tissue damage. Certain inflammatory chemokines activate cells to initiate an immune response or promote wound healing. Learn More.

Chemokines and Cancer
Chemokines make a critical contribution to a diverse range of physiological and pathological processes including embryogenesis, immune system development and function, inflammation, tumourigenesis and cancer metastasis. A complex network of chemokines and their receptors influences the development of primary tumours and cancer metastases. New information about the biological role of chemokines in these cancer related processes is providing insights into host–tumour interactions, such as the role of the leukocyte infiltrate, and into the mechanisms that determine the metastatic potential and site-specific spread of cancer cells. Chemokine-receptor antagonists are showing promise in animal models of inflammation and autoimmune disease. Chemokines are chemotactic cytokines that cause the directed migration of leukocytes, and are induced by inflammatory cytokines, growth factors and pathogenic stimuli. Learn More.

Chemokines and Cytokines
Chemokines (movement, Greek -kinos ) belong to a family of cytokines , and they are small proteins secreted by cells. The name is derived from their function to induce directed chemotaxis in nearby responsive cells; they are chemotactic cytokines. Learn More.

Chemokine & Receptor References
  1. Larry C, et al. (2003) Cytokines and chemokines. J Allergy Clin Immunol. 111(2 Suppl):S460-75.
  2. Guerreiro R, et al. (2011) The chemokines and their receptors: characteristics and physiological functions. Acta Med Port. 24 Suppl 4:967-76.
  3. Laing K, et al. (2004). Chemokines. Dev Comp Immunol. 28 (5): 443–60.
  4. Fran B, et al. (2004) Cancer and the chemokine network. Nature Reviews Cancer. 4, 540-550.
  5. Larry C, et al. (2003) Cytokines and chemokines. J Allergy Clin Immunol. 111(2 Suppl):S460-75.
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