Growth Factors and Tyrosine Kinase Receptors

Abstract

Signalling pathways originating from the interaction between growth factors (GF) and tyrosine kinase receptors (TKRs) are certainly the best known because of their leading role in oncogenesis. These pathways are multiple and will be studied in several chapters; the present chapter exclusively concerns GFs and TKRs, whereas Chaps. 2 and 3 will present two major signalling pathways downstream these interactions. We adopt here a definition of ‘growth factors’ restricted to those activating TKRs. Other classes of receptors will be studied in other chapters: receptors activating cytoplasmic tyrosine kinases (Chap. 4), serine/threonine kinase receptors (Chap. 5), etc.

More than 100 GF and 58 TKRs, distributed among 20 families, have been identified and a large part of them may play a role in oncogenesis. Activation of TKRs occurs according to a unique mechanism, involving dimerisation and autophosphorylation of the receptors, through their own tyrosine kinase activity, and constitutes the starting point of the signalling pathway. These dimeric associations of TKRs establish the link between GFs and cellular response; there exists a complex combinatorial pattern of these associations, which determines the type of action exerted on the cell receiving the signal. The number of possible combinations is high, which explains why the same signal may generate distinct consequences in the target cells: for instance, proliferation and differentiation may be induced by the same signal acting on different cells. Lastly, the signalling pathways downstream the GF–TKR interaction are multiple and depend upon the proteins expressed by the target cell, which is often referred to as ‘the cellular context’.