TY - JOUR
T1 - Cracking the context-specific PI3K signaling code
AU - Madsen, Ralitsa R.
AU - Vanhaesebroeck, Bart
N1 - Funding Information:
We are grateful to R. Semple, B. Bilanges, S. Conduit, L. Gerosa, and J. Longden for their helpful feedback during the preparation of this manuscript. Work in the laboratory of B.V. is supported by PTEN Research, Cancer Research UK (C23338/ A25722), the UK Biotechnology and Biological Sciences Research Council (BB/I007806/1, BB/ M013278/1, and BB/R017972/1), and the UK NIHR University College London Hospitals Biomedical Research Centre.
Publisher Copyright:
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works
PY - 2020/1/7
Y1 - 2020/1/7
N2 - Specificity in signal transduction is determined by the ability of cells to “encode” and subsequently “decode” different environmental signals. Akin to computer software, this “signaling code” governs context-dependent execution of cellular programs through modulation of signaling dynamics and can be corrupted by disease-causing mutations. Class IA phosphoinositide 3-kinase (PI3K) signaling is critical for normal growth and development and is dysregulated in human disorders such as benign overgrowth syndromes, cancer, primary immune deficiency, and metabolic syndrome. Despite decades of PI3K research, understanding of context-dependent regulation of the PI3K pathway and of the underlying signaling code remains rudimentary. Here, we review current knowledge on context-specific PI3K signaling and how technological advances now make it possible to move from a qualitative to quantitative understanding of this pathway. Insight into how cellular PI3K signaling is encoded or decoded may open new avenues for rational pharmacological targeting of PI3K-associated diseases. The principles of PI3K context-dependent signal encoding and decoding described here are likely applicable to most, if not all, major cell signaling pathways.
AB - Specificity in signal transduction is determined by the ability of cells to “encode” and subsequently “decode” different environmental signals. Akin to computer software, this “signaling code” governs context-dependent execution of cellular programs through modulation of signaling dynamics and can be corrupted by disease-causing mutations. Class IA phosphoinositide 3-kinase (PI3K) signaling is critical for normal growth and development and is dysregulated in human disorders such as benign overgrowth syndromes, cancer, primary immune deficiency, and metabolic syndrome. Despite decades of PI3K research, understanding of context-dependent regulation of the PI3K pathway and of the underlying signaling code remains rudimentary. Here, we review current knowledge on context-specific PI3K signaling and how technological advances now make it possible to move from a qualitative to quantitative understanding of this pathway. Insight into how cellular PI3K signaling is encoded or decoded may open new avenues for rational pharmacological targeting of PI3K-associated diseases. The principles of PI3K context-dependent signal encoding and decoding described here are likely applicable to most, if not all, major cell signaling pathways.
UR - http://www.scopus.com/inward/record.url?scp=85077720602&partnerID=8YFLogxK
U2 - 10.1126/scisignal.aay2940
DO - 10.1126/scisignal.aay2940
M3 - Review article
C2 - 31911433
AN - SCOPUS:85077720602
SN - 1945-0877
VL - 13
JO - Science Signaling
JF - Science Signaling
IS - 613
M1 - eaay2940
ER -