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EGFR Signaling Networks in Cancer Therapy pp 91–111Cite as

PHOSPHOINOSITIDE 3-KINASE ENZYMES AS DOWNSTREAM TARGETS OF THE EGF RECEPTOR

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Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

Phosphoinositide 3-kinase (PI3K) activity plays a critical role downstream of the activated epidermal growth factor receptor (EGFR), regulating cell viability, proliferation, and migration. Here I will overview the components of the PI3K signaling pathway and its control. Emphasis is placed on the eight PI3K catalytic isoforms expressed in human tissue and grouped into three classes termed I, II, and III based on sequence similarity and substrate specificity. The nature and localization of the 3-phosphoinositide products of PI3K activity govern the translocation/activation of protein targets that include the serine/threonine kinases Akt and PDK-1. In this way the EGFR elicits its spectrum of intracellular effects that include altering cell migration, vesicle transport, cell cycle progression, metabolism, and transcription. Despite the intense focus, the mechanisms by which the activated EGFR stimulates PI3K activity are not completely understood. In addition, the possibility of EGF stimulated synthesis of phosphatidylinositol (3) phosphate could provide exciting new insights into the regulation of EGFR mediated vesicle transport.

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Domin, J. (2008). PHOSPHOINOSITIDE 3-KINASE ENZYMES AS DOWNSTREAM TARGETS OF THE EGF RECEPTOR. In: Haley, J., Gullick, W. (eds) EGFR Signaling Networks in Cancer Therapy. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59745-356-1_8

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