Growth factors trigger local and long distance signalling

Growth factors trigger local and long distance signalling. In the cell body, various growth factors, such as NGF and EGF, trigger the activation of the MAPK pathway. After the activation of TrkA (shown in blue) several positive feedback loops induce persistent MAPK signalling, causing cell differentiation. Rab GTPases regulate endosomal dynamics and signalling; for example, internalization of TrkA receptor in Rab5-positive endosomes, acts as a positive feedback loop for TrkA signalling, as shown by S. Halegoua (New York, NY, USA). Conversely, EGFR (red) is rapidly internalized to Rab7-positive endosomes in a process regulated by ubiquitination, in which EGFR signalling is rapidly downregulated. Both EGFR and TrkA are ubiquitinated and can signal from early endosomes (EE). However, how ubiquitination regulates TrkA endocytosis and why the signalling of both receptors from EE is different is still a matter of debate (see ). In distal parts of the cells, such as axons in neurons, growth factor signalling might be transmitted to the cell body by using phosphorylation waves (small red arrows) or motor-regulated vesicle transport of a signalling endosome. EGFR, epidermal growth factor receptor; imp-β, importin-β; LE/L, late endosome/lysosome; MAPK, mitogen-activated protein kinase; NGF, nerve growth factor; PKC, protein kinase C; TrkA, tyrosine kinase A receptor.

Publication

Commuting within the cell—mind the GAPs. Workshop on Systems Dynamics of Intracellular Communication:Overcoming Distance in Signalling Networks. (2007) Francisca C. Bronfman, et al. EMBO Rep. 2007 Nov;8(11):1011-1015. Figure: F2. Homo sapiens

Disease mentions