NDLI: Agonist-stimulated phosphatidylinositol-3,4,5-trisphosphate generation by scaffolded phosphoinositide kinases

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Agonist-stimulated phosphatidylinositol-3,4,5-trisphosphate generation by scaffolded phosphoinositide kinases

Content Provider	Semantic Scholar
Author	Choi, Suyong Hedman, Andrew C. Sayedyahossein, Samar Thapa, Narendra Sacks, David B. Anderson, Richard A.
Copyright Year	2016
Abstract	Generation of the lipid messenger phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) is crucial for development, cell growth and survival, and motility, and it becomes dysfunctional in many diseases including cancers. Here we reveal a mechanism for PtdIns(3,4,5)P3 generation by scaffolded phosphoinositide kinases. In this pathway, class I phosphatidylinositol-3-OH kinase (PI(3)K) is assembled by IQGAP1 with PI(4)KIIIα and PIPKIα, which sequentially generate PtdIns(3,4,5)P3 from phosphatidylinositol. By scaffolding these kinases into functional proximity, the PtdIns(4,5)P2 generated is selectively used by PI(3)K for PtdIns(3,4,5)P3 generation, which then signals to PDK1 and Akt that are also in the complex. Moreover, multiple receptor types stimulate the assembly of this IQGAP1–PI(3)K signalling complex. Blockade of IQGAP1 interaction with PIPKIα or PI(3)K inhibited PtdIns(3,4,5)P3 generation and signalling, and selectively diminished cancer cell survival, revealing a target for cancer chemotherapy.
Starting Page	1324
Ending Page	1335
Page Count	12
File Format	PDF HTM / HTML
DOI	10.1038/ncb3441
PubMed reference number	27870828
Journal	Medline
Volume Number	18
Alternate Webpage(s)	https://anderson.research.labs.wisc.edu/pdf/Agonist-stimulated%20phosphatidylinositol-%203,4,5-trisphosphate%20generation%20by%20scaffolded%20phosphoinositide%20kinases.pdf
Alternate Webpage(s)	https://doi.org/10.1038/ncb3441
Journal	Nature Cell Biology
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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