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Sci. STKE, 26 February 2002
Vol. 2002, Issue 121, p. tw81
[DOI: 10.1126/stke.2002.121.tw81]


Receptor Endocytosis Regulating Signals in Cellular Time and Space

Signals detected at the extracellular side of a cell's plasma membrane are transduced into the cell through the activation of transmembrane receptors and intracellular signaling proteins. Often signals are attenuated by endocytosis of receptors into endosomal vesicles. However, recent evidence indicates that endocytosis does not necessarily extinguish all signals that emanate from receptors. Haugh and Meyer now show that the epidermal growth factor receptor (EGFR) can signal from endosomes; however, the capacity of the receptors to signal is modified. By using chimeric proteins that specifically recognize phosphotyrosine, phosphatidylinositol-4,5-bisphosphate (PIP2), or phosphatidylinositol-3,4,5-trisphosphate (PIP3), the authors found that phosphorylated (activated) EGFRs were detected in endosomes but neither phosphoinositide-specific probe associated with endosomes. These data suggest that neither PIP2 [a substrate for phospholipase (PLC-{gamma})] nor PIP3 [a product of phosphatidylinositol 3'-kinase (PI3K), whose enzymatic activity is important for cell proliferation] resides in the endosomal compartment and that EGFR-dependent signaling from endosomes does not activate signal pathways involving these two enzymes. These findings also suggest a mechanism whereby the duration and location of specific subsets of intracellular signals can be regulated and separated from other subsets of signals.

J. M. Haugh, T. Meyer, Active EGF receptors have limited access to PtdIns(4,5)P2 in endosomes: implications for phospholipase C and PI 3-kinase signaling. J. Cell Sci. 115, 303-310 (2002). [Online Journal]

Citation: Regulating Signals in Cellular Time and Space. Sci. STKE 2002, tw81 (2002).

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