Receptor Endocytosis and Compartmentalized Intracellular Signaling

For his graduate thesis, Prof. Haugh studied the effects of epidermal growth factor (EGF) receptor internalization on the magnitude and specificity of intracellular signaling. This topic is currently not a major focus of our laboratory, but the interested reader is referred to the following publications.

Haugh JM (2002). Localization of receptor-mediated signal transduction pathways: the inside story. Molecular Interventions, 2: 292-307 (Review). 

Haugh JM, Meyer T (2002). Active EGF receptors have limited access to PI(4,5)P2 in endosomes: implications for phospholipase C and PI 3-kinase signaling. Journal of Cell Science, 115: 303-310. 

Haugh JM, Huang AC, Wiley HS, Wells A, Lauffenburger DA (1999). Internalized epidermal growth factor receptors participate in the activation of p21(ras) in fibroblasts. Journal of Biological Chemistry, 274: 34350-34360. 

Haugh JM, Schooler K, Wells A, Wiley HS, Lauffenburger DA (1999). Effect of epidermal growth factor receptor internalization on regulation of the phospholipase C-γ1 signaling pathway. Journal of Biological Chemistry, 274: 8958-8965. 

Haugh JM, Lauffenburger DA (1998). Analysis of receptor internalization as a mechanism for modulating signal transduction. Journal of Theoretical Biology, 195: 187-218. 

Lauffenburger, D.A., Fallon, E.F. and Haugh, J.M. (1998). Scratching the (cell) surface: cytokine engineering for improved ligand/receptor trafficking dynamics. Chemistry & Biology, 5: R257-R263 (Review). 

Cartoon of compartmentalized receptor signaling, most resembling the epidermal growth factor (EGF) receptor system. Hydrolysis and phosphorylation of phosphatidylinositol (4,5)-bisphosphate (PIP2) by phospholipase C (PLC) and phosphoinositide 3-kinase (PI3K), respectively, are restricted to the plasma membrane. Internalized receptors, insofar as they remain ligated, retain the ability to recruit those enzymes, but PIP2 is not accessible to them in endosomal membranes. On the other hand, surface and internalized receptor-ligand complexes contribute equally to the production of Ras-GTP. Adapted from the Molecular Interventions review.