The last fifteen years have seen an explosive progress in our knowledge of how cell proliferation and differentiation are regulated by extracellular factors. A few growth factors were initially characterized following extensive purification and are now often considered as prototypes for families of structurally related factors. Concomitant with their characterization came the recognition that these related factors mediate their activities through a large number of cell surface receptors, which based on structural features, can also be divided in families. Most receptors for growth stimulatory factors are cell surface transmembrane proteins that either contain a cytoplasmic tyrosine kinase domain or associate with a cytoplasmic tyrosine kinase. Ligand-induced autophosphorylation of these kinases on tyrosines then initiates the signaling cascades that lead to altered cell proliferation. Usually, structurally related growth factors interact with structurally related receptors and distinct receptor families generally mediate activities of families of growth factors. Thus, the combinatorial interactions between multiple growth factors and receptors are likely to result in the transfer of a complex body of information through multiple signaling cascades into the nucleus, where consequent changes in cell proliferation and differentiation and in gene Ž w x. transcription are initiated for reviews: 1–7. The rapid progress in our knowledge of growth factors and their receptors is well illustrated by the characterization of a superfamily of growth factors Ž related to transforming growth factor-ß the TGF-ß