The interface of receptor trafficking and signalling

The intimate relationship between receptor trafficking and signalling is beginning to reveal its secrets. Receptor endocytosis provides a mechanism for attenuation of signalling by transfer of receptors to degradative compartments. However, it can also determine signalling output by providing a different combination of downstream effectors at endocytic compartments compared with the plasma membrane. Rab5, Hrs and Cbl, are three examples of proteins that can influence both tyrosine kinase receptor trafficking and signalling pathways. By operating at this intersection, they are well placed to couple these aspects of cell function. Each element of the Rab5 GTPase cycle is influenced by signal transduction events, which will correspondingly influence recruitment of effector proteins and receptor distribution. Hrs and Cbl, which both undergo tyrosine phosphorylation in response to growth factor stimulation, are believed to influence receptor sorting in the early endosome and engage in multiple interactions, which may play a direct role in signalling cascades.