Abstract
Signals transduced from ligand-activated receptor tyrosine kinases (RTKs) lead to a diverse array of biological outcomes, such as cell proliferation. Strict regulation of RTK activity is therefore necessary to prevent aberrancies in cell signaling that can lead to diseases such as cancer. RTKs are activated at the plasma membrane (PM) upon ligand binding. Contrary to the initial belief, RTK activity does not terminate immediately following endocytosis, instead RTKs remain active while being trafficked in endosomes. Here we describe a two-pulse endosomal stimulation approach which can specifically activate endosome-accumulated EGFR and drive cell proliferation.
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References
Jiang G, Hunter T (1999) Receptor signaling: when dimerization is not enough. Curr Biol 9(15):R568–R571
Schlessinger J, Ullrich A (1992) Growth factor signaling by receptor tyrosine kinases. Neuron 9(3):383–391
Schlessinger J (1986) Allosteric regulation of the epidermal growth factor receptor kinase. J Cell Biol 103(6 Pt 1):2067–2072
Burke P, Schooler K, Wiley HS (2001) Regulation of epidermal growth factor receptor signaling by endocytosis and intracellular trafficking. Mol Biol Cell 12(6):1897–1910
Wiley HS, Burke PM (2001) Regulation of receptor tyrosine kinase signaling by endocytic trafficking. Traffic 2(1):12–18
Wang Y, Pennock SD, Chen X, Kazlauskas A, Wang Z (2004) Platelet-derived growth factor receptor-mediated signal transduction from endosomes. J Biol Chem 279(9):8038–8046
Wang Y, Pennock S, Chen X, Wang Z (2002) Internalization of inactive EGF receptor into endosomes and the subsequent activation of endosome-associated EGF receptors. Epidermal growth factor. Sci STKE 2002(161):pl17
Wang Y, Pennock S, Chen X, Wang Z (2002) Endosomal signaling of epidermal growth factor receptor stimulates signal transduction pathways leading to cell survival. Mol Cell Biol 22(20):7279–7290
Pennock S, Wang Z (2008) A tale of two Cbls: interplay of c-Cbl and Cbl-b in epidermal growth factor receptor downregulation. Mol Cell Biol 28(9):3020–3037
Pennock S, Wang Z (2003) Stimulation of cell proliferation by endosomal epidermal growth factor receptor as revealed through two distinct phases of signaling. Mol Cell Biol 23(16):5803–5815
Kourouniotis G, Wang Y, Pennock S, Chen X, Wang Z (2016) Non-ligand-induced dimerization is sufficient to initiate the signalling and endocytosis of EGF receptor. Int J Mol Sci 17(8):1200
Jones SM, Kazlauskas A (2000) Connecting signaling and cell cycle progression in growth factor-stimulated cells. Oncogene 19(49):5558–5567
Jones SM, Kazlauskas A (2001) Growth factor-dependent signaling and cell cycle progression. FEBS Lett 490(3):110–116
Jones SM, Kazlauskas A (2001) Growth-factor-dependent mitogenesis requires two distinct phases of signalling. Nat Cell Biol 3(2):165–172
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Pennock, S., Billing, S., Wang, Z., Wang, Y. (2017). Two-Pulse Endosomal Stimulation of Receptor Tyrosine Kinases Induces Cell Proliferation. In: Wang, Z. (eds) ErbB Receptor Signaling. Methods in Molecular Biology, vol 1652. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7219-7_9
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DOI: https://doi.org/10.1007/978-1-4939-7219-7_9
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Publisher Name: Humana Press, New York, NY
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Online ISBN: 978-1-4939-7219-7
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