Polypeptide growth factors are hormone-like modulators of cell proliferation and differentiation in vitro and in vivo. These functions are mediated, in part, by interaction of the growth factors with relatively high-affinity cell-surface receptors and subsequent alterations in gene expression within responsive cells. The complete cascade of signals initiated by growth factor occupancy of cell-surface receptors that are responsible for the mitogenic or differentiating responses are not known. However, activation of tyrosine kinases, changes in cyclic nucleotide metabolism, inositol-3-phosphate levels, and intracellular free calcium levels are thought to be the mediators of polypeptide growth factor action. Abnormal regulation of one or more of these signal pathways may explain the mechanism of action of cellular oncogenes and resulting phenotypes associated with cellular transformation. The previous review in this series by James & Bradshaw (1) is likely to be the last comprehensive article on polypeptide growth factors. We focus this review on the structures and functions associated with the fibroblast or heparin-binding growth factor (HBGF) family of polypeptides. We refer the reader to the following references for recent reviews of other polypeptide growth factors: epidermal growth factor (2), nerve growth factor (1), plateletн derived growth factors (3, 4), insulin-like growth factors (5), transforming growth factors (6--8), hematopoietic growth factors (9), and their receptors (10--12).

The HBGF family presently consists of five structurally related polypeptides. The genes for each have been cloned and sequenced. Two of the members, HBGF-l and HBGF-2, have been characterized under many different names (see below), but most often as acidic and basic fibroblast growth factor, respectively. Three recent additions to the family are oncogene products of related sequence. The normal gene products influence the general proliferation capacity of the majority of mesoderm-and neuroectodermн derived cells. They are capable of inducing angiogenesis in vivo and may play important roles in early development. Although little is known about the true physiological functions of these proteins or their mechanism of action, the cloning of their genes, the identification of their receptors, and the identificaн tion of related oncogenes should provide the experimental basis to increase our understanding of these important areas.