Direct Binding and Activation of Receptor Tyrosine Kinases by Collagen

Receptor tyrosine kinases play an important role in the control of cell growth, differentiation, metabolism, and cell migration among many other biological responses. To date, more than sixteen families of receptor tyrosine kinase have been identified. The first receptor tyrosine kinases were identified as the cell surface receptors that transduce the intracellular signals of growth factors, such as epidermal growth factor (EGF) or hormones such as insulin (Schlessinger and Ullrich 1992). All receptor tyrosine kinases exhibit similar molecular architecture and are activated by a common mechanism. This large receptor family is characterized by an extracellular ligand-binding domain, a single transmembrane region, and a cytoplasmic domain that contains a conserved catalytic protein tyrosine kinase core and sequences responsible for positive and negative receptor regulation (Schlessinger and Ullrich 1992).