Signal Transduction through Growth Factor Receptors

Includes some chapters that deal with two tyrosine kinase receptors (receptors for insulin and hepatocyte growth factor), six receptors (for IL-3, IL-5, IL-6, G-CSF, GM-CSF, and erythropoietin) in a new receptor family, and one unique receptor (IL-1 receptor) that does not belong to any known receptor family.

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Intense interest has been focused on the proliferation and differentiation of cells in multicellular organisms, because these events play a key role in embryogenesis, and coordinate the development and maintenance of the whole body by recruiting the mature cells with specific functions and regulating the formation of organs.
Proteins, called growth factors, are mainly responsible for determining the fate of cells. The actions of growth factors are mediated by their interaction with specific receptors composed of an extracellular ligand-binding portion, a membrane spanning region, and a cytoplasmic region. The most important question is: How is the interaction of a ligand with its receptor transferred through the cytoplasmic membrane into the intracellular machinery that governs cell behavior? Tremendous efforts devoted to cloning growth factor receptors have made it possible to dissect receptor structures into functional domains: a ligand-binding site, a signal transducer region, and a regulatory domain.
The first exciting finding was that receptors for epidermal growth factor (EGF), insulin, insulin-like growth factor (JGF), platelet-derived growth factor (PDGF), and several other growth factors were tyrosine kinases that were regulated by binding to individual specific ligands; the receptors are membrane-associated allosteric enzymes. In addition to the tyrosine kinase receptor family, a new receptor family has recently been found which has no tyrosine kinase domain, but has two characteristic conserved features (two pairs of cysteines and a Trp-Ser-X-Trp-Ser motif) in the extracellular region. Receptors of prolactin, growth hormone, and several hemopoietic growth factors including IL-2, IL-3, IL-5, IL-6, granulocyte colony-stimulating factor (G-CSF), granulocyte/macrophage colony-stimulating factor (GM-CSF), and erythropoietin belong to this new family.
Some chapters selected for this volume deal with two tyrosine kinase receptors (receptors for insulin and hepatocyte growth factor), six receptors (for IL-3, IL-5, IL-6, G-CSF, GM-CSF, and erythropoietin) in a new receptor family, and one unique receptor (IL-1 receptor) that does not belong to any known receptor family. Emphasis on a new receptor family is possible because of remarkable progress in the elucidation of receptor compnents that construct high-affinity ligand binding sites and signal transducers.
Although we are still far from a full understanding of the molecular bases connecting ligand binding with cell behavior, the editors believe that one can appreciate through these authoritative reviews where the field is now and where it is proceeding in the years ahead.