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.
Clague
M J
MJ
Physiological Laboratory, University of Liverpool, Crown St., Liverpool L69 3BX, UK. clague@liv.ac.uk
Urbé
S
S
D000818:Animals; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D029721:Drosophila Proteins; D004705:Endocytosis; D056827:Endosomal Sorting Complexes Required for Transport; D011992:Endosomes / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism; D008954:Models, Biological; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D050721:Proto-Oncogene Proteins c-cbl; D015398:Signal Transduction; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism
D029721:Drosophila Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; C096164:hepatocyte growth factor-regulated tyrosine kinase substrate; D050721:Proto-Oncogene Proteins c-cbl; D066246:ErbB Receptors; D020558:GTP Phosphohydrolases; D020696:rab5 GTP-Binding Proteins; C106411:Cbl protein, Drosophila