Chemistry of Life

Molecular genetics, biochemistry

growth factors

Growth factors are naturally occuring proteins responsible for stimulating cellular proliferation and cellular differentiation, and for regulation of a variety of cellular processes. Growth factors, such as cytokines and hormones act as a signaling molecules by binding to specific surface receptors on target cells.

Growth factors promote tissue specific cellular differentiation and maturation – bone morphogenic proteins (BMPs) stimulate bone cell differentiation, while vascular endothelial growth factors (VEGFs) stimulate blood vessel differentiation.

Epidermal growth factor (EGF) regulates cellular differentiation, growth, and proliferation. It acts by binding with high affinity to epidermal growth factor receptors (EGFRs), which possess intrinsic tyrosine kinase activity (autophosphorylation). The epidermal growth factor (EGFR) family of receptor tyrosine kinases comprises four receptors: EGF-R (ErbB1), ErbB2 (Neu), ErbB3, and ErbB4. The binding of EGF to EGFRs stimulates a signal transduction cascade that causes altered cellular activity, including a rise in intracellular glycolysis, increased protein synthesis, and increases in gene expression (including the gene for EGFR). The signaling cascade ultimately leads to DNA synthesis and cell proliferation. [1]

Nerve growth factor (NGF) is critical for the survival and maintenance of sympathetic and sensory neurons, and is secreted by the neuron's target cell. NGF activates the neuron's high affinity receptor (TrkA) and the NGF/TrkA complex is internalized by the responding neuron and transported to the soma. NGF also binds to the low affinity nerve growth factor receptor (LNGFR).

Nerve growth factor is a pain-evoking mediator, which along with proinflammatory cytokines, chemokines, protons, and prostaglandins is produced by invading leukocytes or by local cells.

Platelet-derived growth factor (PDGF) is a ubiquitous, potent mitogen and chemotactic factor for many connective tissue cells. PDGF occurs as a three-disulfide-linked dimer composed of two homologous chains, α and β (1,2). The biological function of PDGF is mediated through binding to two cell surface proteins, PDGF receptors α and ß (35). Binding of PDGF to the extracellular part of either receptor type leads to dimerization of receptor molecules, followed by activation of the receptor protein-tyrosine kinase (6) and generation of phosphorylation-mediated signals that initiate the biological response (7,8).

PDGF has been implicated in the pathogenesis of several non-malignant proliferative diseases including atherosclerosis (2324), fibrosis (25), restenosis following vascular angioplasty (26), giant cell arteritis (27), aseptic loosening (28) and bronchiolitis obliterans syndrome (29). [3]

· adenylyl (adenylate) cyclase ·· C · Cadherins · calcium ions · cAMP-dependent protein kinase · CDKs · cellular adhesion · cyclin-dependent kinases · cytokines ·· D · DAG · diacylglycerol · DNA ligases ·· E · ERKs ·· F · focal adhesion kinases ·· G · GPCRs · GPCR families · guanylate cyclases · guanyl cyclase ·· I · Immunoglobulins · Integrins · inositol triphosphate · IP3 ·· M · MAP kinases · mitogen activated protein kinases ·· P · phosphatases · phosphodiesterases · phospolipases · phosphorylation · PKA · PKC · phospholipase C-gamma · protein kinase A · protein kinase C · protein tyrosine kinases (PTKs) ·· R · receptor tyrosine kinases · Rho GTPases ·· S · second messengers · second messenger cAMP · second messenger cGMP · Selectins · signal transduction ·· T · tfs . general transcription factors . upstream transcription factors . inducible transcription factors . transcription binding protein · two-component systems ··

 Cell Adhesion Molecules  Cell signaling  Immune Cytokines  Second Messengers  Regulatory Proteins Sequences  Electron Transport Chain vs Oxidative Phosphorylation  Enzymes Function Krebs Cycle  Enzymes Cofactors of Krebs Cycle  Phosphate-handling enzymes  Gene Regulation in E.coli 

. Epidermal Growth Factor (EGF) . Platelet-Derived Growth Factor (PDGF) . Fibroblast Growth Factors (FGFs) . Transforming Growth Factors-b TGFs-b) . Transforming Growth Factor-a (TGF-a) . Erythropoietin (Epo) . Insulin-Like Growth Factor-I (IGF-I) . Insulin-Like Growth Factor-II (IGF-II) . Interleukin-1 (IL-1) . Interleukin-2 (IL-2) . Interleukin-6 (IL-6) . Interleukin-8 (IL-8) . Tumor Necrosis Factor-a (TNF-a) . Tumor Necrosis Factor-b (TNF-b)
Interferon-g (INF-g) . Colony Stimulating Factors (CSFs) .



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. . . transcription begun 10/06/06