Polypeptide growth factors

The term cytokine was first introduced in the mid 1970s. It was applied to polypeptide growth factors controlling the differentiation and regulation of cells of the immune system. The interferons and interleukins represented the major polypeptide families classified as cytokines at that time. Additional classification terms were also introduced, including lymphokines (cytokines such as IL-2 and IFN-y, produced by lymphocytes) and monokines (cytokines such as TNF-a, produced by monocytes). However, classification on the basis of producing cell types also proved inappropriate, as most cytokines are produced by a range of cell types (e.g. both lymphocytes and monocytes produce IFN-a). 

The differentiation, growth and division of eukaryotic cells is modulated by various influences, of which growth factors are amongst the most important for many cell types. A wide range of polypeptide growth factors have been identified (Table 10.1) and more, undoubtedly, remain to be characterized. Factors that inhibit cell growth also exist. For example, interferons and TNF inhibit proliferation of various cell types. 

Table 10.1 Overview of some polypeptide growth factors. Many can be grouped into families on the basis of amino acid sequence homology, or the cell types affected. Most growth factors are produced by more than one cell type and display endocrine, paracrine or autocrine effects on target cells by interacting with specific cell surface receptors...

Faroni RE and DeCupis A. The role of polypeptide growth factors in human carcinomas New targets for a novel pharmacological approach. Pharmacol Rev 2000 52 179-206. 

Arcaro, A. Zvelebil, M.J. Wallasch, C. Ullrich, A. Waterfield, M.D. Dom-in, J. Class II phosphoinositide 3-kinases are downstream targets of activated polypeptide growth factor receptors. Mol. Cell. Biol., 20, 3817-3830 (2000)... 

Some cell lines, such as Namalwa, can grow satisfactorily in medium in which the only protein is albumin. Other cell lines show distinct protein requirements, such as albumin, transferrin, and insulin, or the addition of polypeptide growth factors, isolated from non-serum sources that have shown stimulation of many cell types in culture. Some cells have very fastidious growth requirements and their stability and productivity may be reduced significantly in serum-free media. 

FGFs constitute a large family of structurally related polypeptide growth factors that signal through receptor tyrosine... 

Renner U, Fagotto U, Arzt E, Stalla GK. Autocrine and paracrine roles of polypeptide growth factors, cytokines and vasogenic substances in normal and tumorous pituitary function and growth A review. Eur J Endocrinol 1996 135 515-32. 

The neurotrophins are unusual among polypeptide growth factors in that two different transmembrane proteins serve as receptors for each neurotrophin. The structural features of Trk tyrosine kinases and the p75 neurotrophin receptor are displayed in Fig. 1. The Trk subfamily of receptor tyrosine kinases is distinguished by immunoglobulin-C2 domains and repeats rich in leucine and cysteine residues in the extracellular domain and a tyrosine kinase domain with a small interruption and a short cytoplasmic tail. 

Abboud HE, Woodruff KA, Snyder SP, Bonewald LF. Polypeptide growth factors regulate the production of latent transforming growth factor B in human mesangial cells. J Am Soc Nephrol 1991 2 434. 

Most studies of mammalian cell-cycle control have been done with cultured cells that require certain polypeptide growth factors (mitogens) to stimulate cell proliferation. 

Various polypeptide growth factors called mitogens stimulate cultured mammalian cells to proliferate by inducing expression of early-response genes. Many of these encode transcription factors that stimulate expression of delayed-response genes encoding the Gj CDKs, Gj cycllns, and E2F transcription factors. 

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