Growth factor
Any of a group of biologically active polypeptides which function as hormonelike regulatory signals, controlling the growth and differentiation of responsive cells. Indeed, the distinction between growth factors and hormones is frequently arbitrary and stems more from the manner of their discovery than from a clear difference in function. The discovery of growth factors has been primarily a direct result of the development of techniques for animal-cell culture.
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Home >> Molecular Biology Dictionary >> Growth Factor
Nerve growth factor appears to function in promoting survival of, and extension of, axons from nerve cells of the peripheral nervous system. For example, injection of nerve growth factor into newborn mice causes excessive axon growth from sympathetic and sensory nerve cells, while injection of antiserum to nerve growth factor causes these nerve cells to die. The mouse-gland protein which has been most fully characterized exists as a 136,000-molecular-weight aggregate of µ, b, and g subunits. The b subunit, which consists of two noncovalently associated 13,000-molecular-weight peptide chains, contains the full nerve growth factor activity, while the g subunit is a proteolytic enzyme which is closely related to glandular kallikrein. Epidermal and transforming growth factors Epidermal growth factor, like nerve growth factor, is produced in large amounts in the submaxillary gland of male mice (a fact of uncertain physiological consequence) but is apparently produced by other tissues also. Submaxillary-gland epidermal growth factor, like nerve growth factor, is found in a high molecular-weight aggregate. The 60,000-molecular-weight epidermal growth factor aggregate contains the 6000molecular-weight biologically active subunit, as well as a kallikrein-like proteolytic enzyme which is very similar to, but distinct from, the subunit of nerve growth factor. Both epidermal growth factor and nerve growth factor are produced by proteolytic cleavage of large precursor proteins, and it appears that the kallikrein-like enzymes perform this function. Epidermal growth factor injected into newborn mice causes premature opening of eyelids and eruption of incisors, suggesting that epidermal growth factor normally functions in promoting growth of epithelial tissue. Transforming growth factors are a family of factors with similar biological activity. Several transforming growth factors have been shown to be structurally related to epidermal growth factor (illus. a and b). Transforming growth factors are secreted by a variety of cultured cells, particularly tumor cells, and have the property of causing normal fibroblasts to behave like tumor cells. Consistent with their structural similarity to epidermal growth factor, some transforming growth factors will interact with the epidermal growth factor cell-surface receptor. Somatemedin growth factors Insulinlike growth factors I and II are distinct but similar, differing only in a few amino acids. Somatemedins A and C and multiplication stimulating factor are themselves quite similar to the insulinlike growth factors. They share a number of biological activities, including stimulation of sulfation of cartilage by chondrocytes, stimulation of proliferation of fibroblasts, and insulin is a more distantly related member of this family (illus.c) Nevertheless, the relationship is close enough to permit insulin to bind to somatemedian receptors and, at high concentrations, to stimulate proliferation of fibroblasts. Platelet-derived growth factor This growth factor is stored in blood platelets and is released during blood clotting. Since platelet-derived growth factor stimulates fibroblast cell proliferation tissue cultures, it is likely that release of platelet-derived growth factor at wound sites may be important for stimulation of wound healing. Fibroblast growth factor has not been so fully characterized as platelet-derived growth factor, but while they share many similarities, it appears to be a distinct protein. A broader family While there are no readily apparent structural similarities among epidermal growth factor, platelet-derived growth factor, and insulin, the cell-structure receptor proteins for these growth factors do have remarkable similarities, which suggests that epidermal growth factor, insulin, and platelet-derived growth factor families may themselves be related. The similarity of the receptors lies in the fact that each is a protein kinase (an enzyme which phosphorylates proteins), and the preferred substrate of the receptor kinase activity is the receptor itself. The receptor protein kinase activities are unusual in preferring tyrosine residues in proteins as substrates (most known kinases prefer serine or threnino) The only other tyrosine-specific protein kinases known are tumor-causing proteins produced by ribonucleic acid (RNA) tumor viruses. Growth factors and cancer The stimulation of cell proliferation by several growth factors is similar in some ways to the rapid cell proliferation characteristic of tumor cells. Furthermore, the growth factor receptors are similar to the tumor-causing proteins produced by several RNA tumor viruses. It has been demonstrated that platelet-derived growth factors is virtually identical to the tumor-causing protein of the RNA tumor virus, simian sarcoma virus. Thus, what has long been a subject of speculation can no longer be doubted: some forms of cancer involve improper function of growth factors.
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