Receptors with tyrosine kinase activity

Ullrich, A., and Schlessinger, J. (1990). Signal transduction by receptors with tyrosine kinase activity. Cell 61 203-212. 

The insulin receptor will be discussed here as a prototype of a receptor with tyrosine kinase activity which transmits a hormonal signal. The other major classes of receptors which transmit hormonal signals are the heptahelical, G-protein-coupled receptors and the nuclear receptors for steroid and non-steroid hormones (see Fig. 1.1) they are discussed later. The receptor for the peptide hormone insulin is one of the most extensively studied RTKs (receptors with tyrosine kinase activity). 

RTK. Membrane-bound receptor with tyrosine kinase activity. These receptors pass the membrane only once. On binding ligand they autophosphorylate their own tyrosine residues and form dimers. The phosphorylated tyrosine residues are recognized by intracellular proteins. Examples are growthfactor receptors. 

Insulin exerts its effects by altering the state of phosphorylation of certain intracellular enzymes by a mechanism that does not involve cAMP but that requires specific binding to surface receptors with tyrosine kinase activity. Insulin exerts acute (minutes), delayed-onset (hours), and longterm (days) effects entirely by way of a single receptor. 

Culture filtrates of Streptomyces were screened for inhibitors of tyrosine kinase in the membrane fraction of human epidermoid carcinoma cell line A431. These cells contain a large number of EGF receptors with tyrosine kinase activity on their membrane. One strain was found to produce a novel compound that inhibited tyrosine kinase (Fig. 3). It was named erbstatin (1). Taxonomic studies indicated that the strain producing erbstatin is closely related to Streptomyces viridosporus. 

C. Receptors with tyrosine kinase activity Receptors Coupled to Various Cytosolic Proteins... 

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