EGF (epidermal growth factor) is the founding member of the EGF family of proteins, which also include Amphiregulin (AREG), Betacellulin (BTC), Epiregulin (EPR), HB-EGF, Neuregulins, and others. Members of epidermal growth factor family have highly similar structural and functional characteristics. They have at least one common structural motif, the EGF domain, which consists of six conserved cysteine residues forming three disulfide bonds. The main structure of EGF domain is a two-stranded beta-sheet followed by a loop to a C-terminal short two-stranded sheet. In addition to their EGF domain, the epidermal growth factor family members are characterized by two features: Production of mitogenic responses in EGF-sensitive cells, and high affinity binding to the EGF receptor.
The activity of epidermal growth factor family members is mediated by the epidermal growth factor receptor tyrosine kinases (EGFR/ErbB). Members of the EGFR/ErbB family are made up of an extracellular region or ectodomain that contains approximately 620 amino acids, a single transmembrane spanning region and a cytoplasmic tyrosine kinase domain. The extracellular domain of the EGF receptor is characterized by its capacity to bind EGF and EGF-like ligands with high affinity. Chemically this portion of the receptor contains 10-11 N-linked oligosaccharide chains, high content of half-cystine residues (10%) that could give rise to as many as 25 disulfides. The region between the two half-cystine-rich clusters is involved in ligand binding. The hallmark of the cytoplasmic portion of epidermal growth factor receptor is the sequence defining the tyrosine kinase domain. Near the carboxyl terminus of the receptor are four sites of EGF-dependent autophosphorylation.Epidermal growth factor plays an important role in the regulation of cell growth, proliferation, and differentiation.
|Cytokine & Receptor Information|
Cytokines are a large group of proteins, peptides or glycoproteins that are secreted by specific cells of immune system. Cytokines are a category of signaling molecules that mediate and regulate immunity, inflammation and hematopoiesis. Cytokines are produced throughout the body by cells of diverse embryological origin. Cytokine is a general name; other names are defined based on their presumed function, cell of secretion, or target of action. For example, cytokines made by lymphocytes can also be referred to as lymphokines, while interleukins are made by one leukocyte and act on other leukocytes. And chemokines are cytokines with chemotactic activities.
Cytokines may act on the cells that secrete them (autocrine action), on nearby cells (paracrine action), or in some instances on distant cells (endocrine action).
Several main groups of cytokines include: interleukins, chemokines, interferons, tumor necrosis factors (TNFs), colony-stimulating factors (CSFs), and TGF-beta superfamily members. Interleukins are a group of cytokines that were first seen to be expressed by leukocytes. They modulate inflammation and immunity by regulating growth, mobility and differentiation of lymphoid and other cells. Chemokines are chemotactic cytokines with the ability to induce directed chemotaxis in nearby responsive cells. Stimulated by pro-inflammatory cytokines infected tissues release chemokines, and chemokine gradients induce leukocytes to move between endothelial cells and pass the basement membrane into the infected tissues. Interferons are cytokines which are made and released by the cells of most vertebrates in response to the presence of pathogens (such as viruses, bacteria, or parasites, or tumor cells). Interferons play critical role in host defense mechanisms. The tumor necrosis factor (TNF) superfamily of cytokines act through ligand-mediated trimerization, causing recruitment of several intracellular adaptors to activate multiple signal transduction pathways for cell survival, death, and differentiation. Colony-stimulating factors (CSFs), also called haematopoietic growth factors, are secreted glycoproteins which regulate bone marrow production of circulating red and white cells, and platelets.
An important part of Cytokines’ action on the immune system is to stimulate immune cell proliferation and differentiation. Cytokines involved in this function include interleukin 1 (IL-1), which activates T cells; IL-2, which stimulates proliferation of antigen-activated T and B cells; IL-4, IL-5, and IL-6, which stimulate proliferation and differentiation of B cells; and other cytokines such as, interferon gamma, IL-3, IL-7 and colony-stimulating factor (GM-CSF).
Cytokines act on their target cells by binding specific membrane receptors. The receptors and their corresponding cytokines have been divided into several families based on their structure and activities. Type I cytokine receptors have certain conserved motifs in their extracellular amino-acid domain, and lack an intrinsic protein tyrosine kinase activity. Type II cytokine receptors are multimeric receptors composed of heterologous subunits, and are receptors mainly for interferons. The extracellular domains of type II cytokine receptors share structural similarities in their ligand-binding domain. Some cytokine receptors belong to the immunoglobulin superfamily, such as IL-1R alpha, IL-1R beta, IL-6R alpha, SCFR, c-kit, etc. Other cytokine receptors include TNF receptor family, chemokine receptors, and TGF-beta receptors.
Cytokines have been proved useful in immune-based therapies. For example, interferon-alpha, a cytokine with broad antiviral properties, has been proven to be useful in treating cancers, such as malignant melanoma. Cytokine therapy is not merely a tool of the future. In fact, several cytokine therapies are now routinely used by many people living with HIV.