Cytokines & Chemokines

Epiregulin is a member of the EGF family of growth factors which includes, among others, epidermal growth factor (EGF), transforming growth factor (TGF)-alpha, amphiregulin (ARG), HB (heparin-binding)-EGF, betacellulin, and the various heregulins. It is expressed mainly in the placenta and peripheral blood leukocytes and in certain carcinomas of the bladder, lung, kidney and colon. Epiregulin stimulates the proliferation of keratinocytes, hepatocytes, fibroblasts and vascular smooth muscle cells. It also inhibits the growth of several tumor-derived epithelial cell lines. Human Epiregulin is initially synthesized as a glycosylated 19.0 kDa transmembrane precursor protein, which is processed by proteolytic cleavage to produce a 6.0 kDa mature secreted sequence.

Epiregulin is a member of the EGF family of growth factors which includes, among others, epidermal growth factor (EGF), transforming growth factor (TGF)-alpha, amphiregulin (ARG), HB (heparin-binding)-EGF, betacellulin, and the various heregulins. It is expressed mainly in the placenta and peripheral blood leukocytes and in certain carcinomas of the bladder, lung, kidney and colon. Epiregulin stimulates the proliferation of keratinocytes, hepatocytes, fibroblasts and vascular smooth muscle cells. It also inhibits the growth of several tumor-derived epithelial cell lines. Human Epiregulin is initially synthesized as a glycosylated 19.0 kDa transmembrane precursor protein, which is processed by proteolytic cleavage to produce a 6.0 kDa mature secreted sequence.

At least 23 different variants of IFN-alpha are known. The individual proteins have molecular masses between 19-26 kDa and consist of proteins with lengths of 156-166 and 172 amino acids. All IFN-alpha subtypes possess a common conserved sequence region between amino acid positions 115-151 while the amino-terminal ends are variable. Many IFN-alpha subtypes differ in their sequences at only one or two positions. Naturally occurring variants also include proteins truncated by 10 amino acids at the carboxy-terminal end.

At least 23 different variants of IFN-alpha are known. The individual proteins have molecular masses between 19-26 kDa and consist of proteins with lengths of 156-166 and 172 amino acids. All IFN-alpha subtypes possess a common conserved sequence region between amino acid positions 115-151 while the amino-terminal ends are variable. Many IFN-alpha subtypes differ in their sequences at only one or two positions. Naturally occurring variants also include proteins truncated by 10 amino acids at the carboxy-terminal end.

Platelet-Derived Growth Factor-BB (PDGF-BB) is one of five dimers (PDGF-AA, AB, BB, CC, and DD) formed by 4 different PDGF subunits. In vivo, PDGF-BB is mainly produced in heart and placenta, and predominantly expressed by osteoblasts, fibroblasts, smooth muscle cells, and glial cells. An inactive precursor of PDGF-BB is produced in the endoplasmic reticulum and then activated by a proprotein convertase after secretion. PDGF-BB functions in a paracrine manner and promotes organogenesis, human skeletal development, and wound healing. PDGF-BB also promotes angiogenesis, particularly in the presence of Fibroblast Growth Factor basic. Therefore, PDGF-BB and its related pathways are potential pharmacological targets.

Platelet-Derived Growth Factor-BB (PDGF-BB) is one of five dimers (PDGF-AA, AB, BB, CC, and DD) formed by 4 different PDGF subunits. In vivo, PDGF-BB is mainly produced in heart and placenta, and predominantly expressed by osteoblasts, fibroblasts, smooth muscle cells, and glial cells. An inactive precursor of PDGF-BB is produced in the endoplasmic reticulum and then activated by a proprotein convertase after secretion. PDGF-BB functions in a paracrine manner and promotes organogenesis, human skeletal development, and wound healing. PDGF-BB also promotes angiogenesis, particularly in the presence of Fibroblast Growth Factor basic. Therefore, PDGF-BB and its related pathways are potential pharmacological targets.

Stromal-Cell Derived Factor-1 beta (SDF-1β), also known as SCYB12, PBSF and CXCL12, is an 8.3 kDa, heparin-binding member of the CXC (or alpha) family of chemokines and signal through the CXCR4 receptor. SDF-1α and β are reported to be monomers at neutral pH and physiologic ionic strength, On the cell surface, this may well facilitate SDF-1 interaction with its two receptors, CXCR4 and syndecan4. Heparin sulfate is known to protect SDF-1 from proteolysis, and CXCR4 exists constitutively as a dimer. Among its many functions, CXCL12 is known to influence lymphopoiesis, regulate patterning and cell number of neural progenitors, and promote angiogenesis (12, 13). It also enhances the survival of myeloid progenitor cells

Stromal-Cell Derived Factor-1 beta (SDF-1β), also known as SCYB12, PBSF and CXCL12, is an 8.3 kDa, heparin-binding member of the CXC (or alpha) family of chemokines and signal through the CXCR4 receptor. SDF-1α and β are reported to be monomers at neutral pH and physiologic ionic strength, On the cell surface, this may well facilitate SDF-1 interaction with its two receptors, CXCR4 and syndecan4. Heparin sulfate is known to protect SDF-1 from proteolysis, and CXCR4 exists constitutively as a dimer. Among its many functions, CXCL12 is known to influence lymphopoiesis, regulate patterning and cell number of neural progenitors, and promote angiogenesis (12, 13). It also enhances the survival of myeloid progenitor cells

CCL11 is a potent eosinophil chemoattractant that was originally purified from bronchoalveolar lavage fluid of guinea pigs sensitized by aerosol challenge with ovalbumin. Human CCL11 cDNA encodes a 97 amino acid residue precursor protein from which the aminoterminal 23 amino acid residues are cleaved to generate the 74 amino acid residue mature human CCL11. At the protein sequence level, mature human CCL11 is approximately 60% identical to mature mouse and guinea pig CCL11. Human CCL11 is chemotactic for eosinophils, but not mononuclear cells or neutrophils. The CC chemokine receptor 3 (CCR3) has now been identified to be a specific human CCL11 receptor. CCR3 has also been shown to serve as a cofactor for a restricted subset of primary HIV viruses and binding of CCL11 to CCR3 inhibited infection by the HIV isolates.