Polypeptide growth factors: Structure, function and mechanism of action
| Autor: | Simona Raffioni, Ritsuko Fujii, Hubert Hondermarck, Ralph A. Bradshaw, Michael A. Yarski, Yvonne Y. Wu |
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| Rok vydání: | 1994 |
| Předmět: | |
| Zdroj: | Pure and Applied Chemistry. 66:9-14 |
| ISSN: | 1365-3075 0033-4545 |
| DOI: | 10.1351/pac199466010009 |
| Popis: | Polypeptide growth factors are a diverse group of hormone-like agents that regulate growth and differentiation through cell surface receptors. They are generally represented by homologous families containing several members with distinct overlapping receptor interactions and hence, responsive hue specificities. Similarly, their receptors are also clustered in family groups of sequence-related proteins. The neurotrophin group, characterized by its typical prototypical member nerve growth factor (NGF), has four members which interact variably with three receptors of the family. The activation of their tyrosine bases initiates the characteristic responses. In PC12 cells, stimulation by NGF leads to activation of non-receptor tyrosine bases and several phospholipid dependent pathways. The sum of these signals induce a variety of immediate early response genes that govern the phenotypic response. However, the minimum pathway ( and its essential components) is not yet fully defined. One of the major functions of proteins is to mediate signal transduction. In higher organisms, this complex process utilizes both soluble and membrane bound ligands to initiate the responses and a wide variety of effector molecules, including cell-surface receptors, that are generally ligand specific, and the component of the intracellular machinery that translate the stimulus into the characteristic phenotypic response (ref. 1). Of the many biological responses that are controlled in this fashion, those related to growth are now amongst those that are best studied. In general, these can be subdivided into hyperplastic (increase in cell number) and hypertrophic (increase in cell size), and are, for the most part, controlled by polypeptide growth factors. These substances are basically indistinguishable in their principal functional and mechanistic properties from many of the classic hormones (ref. 2). In the main, they act through specific cell surface receptors that can initiate a variety of intracellular signals invariably involving a spectrum of protein phosphorylations (ref. 3). As with the classical hormone, the polypeptide growth factors are usually relatively small, highly soluble proteins of compact structure. Although some are glycosylated, the majority are not (ref. 4). Most also contain several disulfide bonds which lends further reinforcement to the 3-dimensional structure, and is a feature expected of proteins exported through the endoplasmic reticulum (ref. 5). There is, however, a small but significant subgroup that is devoid of signal peptides and possess only reduced half-cysteine residues, as expected for intracellular proteins. Significant quantities of these agents are often found associated with the extracellular matrix, but the manner in which they reach extracellular compartment is not presently understood. From a functional point of view, polypeptide growth factors can conveniently be divided into four categories (Table 1). The best known group are those which act on tissues and include a broad range of agents with a myriad of responsive target cells. The neurotrophic factors are a more specialized |
| Databáze: | OpenAIRE |
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