Class IA PI3K p110β Subunit Promotes Autophagy through Rab5 Small GTPase in Response to Growth Factor Limitation

Zhixun Dou, Ji An Pan, Hashem A. Dbouk, Lisa M. Ballou, Jennifer L. DeLeon, Yongjun Fan, Juei Suei Chen, Zhimin Liang, Guangpu Li, Jonathan M. Backer, Richard Z. Lin, Wei Xing Zong

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Autophagy is an evolutionarily conserved membrane trafficking process. Induction of autophagy in response to nutrient limitation or cellular stress occurs by similar mechanisms in organisms from yeast to mammals. Unlike yeast, metazoan cells rely more on growth factor signaling for a wide variety of cellular activities including nutrient uptake. How growth factor availability regulates autophagy is poorly understood. Here we show that, upon growth factor limitation, the p110β catalytic subunit of the class IA phosphoinositide 3-kinases (PI3Ks) dissociates from growth factor receptor complexes and increases its interaction with the small GTPase Rab5. This p110β-Rab5 association maintains Rab5 in its guanosine triphosphate (GTP)-bound state and enhances the Rab5-Vps34 interaction that promotes autophagy. p110β mutants that fail to interact with Rab5 are defective in autophagy promotion. Hence, in mammalian cells, p110β acts as a molecular sensor for growth factor availability and induces autophagy by activating a Rab5-mediated signaling cascade.

Original languageEnglish (US)
Pages (from-to)29-42
Number of pages14
JournalMolecular Cell
Volume50
Issue number1
DOIs
StatePublished - Apr 11 2013

Fingerprint

1-Phosphatidylinositol 4-Kinase
Monomeric GTP-Binding Proteins
Autophagy
Intercellular Signaling Peptides and Proteins
Yeasts
Growth Factor Receptors
Guanosine Triphosphate
IA 3
Mammals
Catalytic Domain
Food
Membranes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Dou, Z., Pan, J. A., Dbouk, H. A., Ballou, L. M., DeLeon, J. L., Fan, Y., ... Zong, W. X. (2013). Class IA PI3K p110β Subunit Promotes Autophagy through Rab5 Small GTPase in Response to Growth Factor Limitation. Molecular Cell, 50(1), 29-42. https://doi.org/10.1016/j.molcel.2013.01.022

Class IA PI3K p110β Subunit Promotes Autophagy through Rab5 Small GTPase in Response to Growth Factor Limitation. / Dou, Zhixun; Pan, Ji An; Dbouk, Hashem A.; Ballou, Lisa M.; DeLeon, Jennifer L.; Fan, Yongjun; Chen, Juei Suei; Liang, Zhimin; Li, Guangpu; Backer, Jonathan M.; Lin, Richard Z.; Zong, Wei Xing.

In: Molecular Cell, Vol. 50, No. 1, 11.04.2013, p. 29-42.

Research output: Contribution to journalArticle

Dou, Z, Pan, JA, Dbouk, HA, Ballou, LM, DeLeon, JL, Fan, Y, Chen, JS, Liang, Z, Li, G, Backer, JM, Lin, RZ & Zong, WX 2013, 'Class IA PI3K p110β Subunit Promotes Autophagy through Rab5 Small GTPase in Response to Growth Factor Limitation', Molecular Cell, vol. 50, no. 1, pp. 29-42. https://doi.org/10.1016/j.molcel.2013.01.022
Dou, Zhixun ; Pan, Ji An ; Dbouk, Hashem A. ; Ballou, Lisa M. ; DeLeon, Jennifer L. ; Fan, Yongjun ; Chen, Juei Suei ; Liang, Zhimin ; Li, Guangpu ; Backer, Jonathan M. ; Lin, Richard Z. ; Zong, Wei Xing. / Class IA PI3K p110β Subunit Promotes Autophagy through Rab5 Small GTPase in Response to Growth Factor Limitation. In: Molecular Cell. 2013 ; Vol. 50, No. 1. pp. 29-42.
@article{ad49e4fea8ae4b71b3abf9cd67a5dea3,
title = "Class IA PI3K p110β Subunit Promotes Autophagy through Rab5 Small GTPase in Response to Growth Factor Limitation",
abstract = "Autophagy is an evolutionarily conserved membrane trafficking process. Induction of autophagy in response to nutrient limitation or cellular stress occurs by similar mechanisms in organisms from yeast to mammals. Unlike yeast, metazoan cells rely more on growth factor signaling for a wide variety of cellular activities including nutrient uptake. How growth factor availability regulates autophagy is poorly understood. Here we show that, upon growth factor limitation, the p110β catalytic subunit of the class IA phosphoinositide 3-kinases (PI3Ks) dissociates from growth factor receptor complexes and increases its interaction with the small GTPase Rab5. This p110β-Rab5 association maintains Rab5 in its guanosine triphosphate (GTP)-bound state and enhances the Rab5-Vps34 interaction that promotes autophagy. p110β mutants that fail to interact with Rab5 are defective in autophagy promotion. Hence, in mammalian cells, p110β acts as a molecular sensor for growth factor availability and induces autophagy by activating a Rab5-mediated signaling cascade.",
author = "Zhixun Dou and Pan, {Ji An} and Dbouk, {Hashem A.} and Ballou, {Lisa M.} and DeLeon, {Jennifer L.} and Yongjun Fan and Chen, {Juei Suei} and Zhimin Liang and Guangpu Li and Backer, {Jonathan M.} and Lin, {Richard Z.} and Zong, {Wei Xing}",
year = "2013",
month = "4",
day = "11",
doi = "10.1016/j.molcel.2013.01.022",
language = "English (US)",
volume = "50",
pages = "29--42",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "1",

}

TY - JOUR

T1 - Class IA PI3K p110β Subunit Promotes Autophagy through Rab5 Small GTPase in Response to Growth Factor Limitation

AU - Dou, Zhixun

AU - Pan, Ji An

AU - Dbouk, Hashem A.

AU - Ballou, Lisa M.

AU - DeLeon, Jennifer L.

AU - Fan, Yongjun

AU - Chen, Juei Suei

AU - Liang, Zhimin

AU - Li, Guangpu

AU - Backer, Jonathan M.

AU - Lin, Richard Z.

AU - Zong, Wei Xing

PY - 2013/4/11

Y1 - 2013/4/11

N2 - Autophagy is an evolutionarily conserved membrane trafficking process. Induction of autophagy in response to nutrient limitation or cellular stress occurs by similar mechanisms in organisms from yeast to mammals. Unlike yeast, metazoan cells rely more on growth factor signaling for a wide variety of cellular activities including nutrient uptake. How growth factor availability regulates autophagy is poorly understood. Here we show that, upon growth factor limitation, the p110β catalytic subunit of the class IA phosphoinositide 3-kinases (PI3Ks) dissociates from growth factor receptor complexes and increases its interaction with the small GTPase Rab5. This p110β-Rab5 association maintains Rab5 in its guanosine triphosphate (GTP)-bound state and enhances the Rab5-Vps34 interaction that promotes autophagy. p110β mutants that fail to interact with Rab5 are defective in autophagy promotion. Hence, in mammalian cells, p110β acts as a molecular sensor for growth factor availability and induces autophagy by activating a Rab5-mediated signaling cascade.

AB - Autophagy is an evolutionarily conserved membrane trafficking process. Induction of autophagy in response to nutrient limitation or cellular stress occurs by similar mechanisms in organisms from yeast to mammals. Unlike yeast, metazoan cells rely more on growth factor signaling for a wide variety of cellular activities including nutrient uptake. How growth factor availability regulates autophagy is poorly understood. Here we show that, upon growth factor limitation, the p110β catalytic subunit of the class IA phosphoinositide 3-kinases (PI3Ks) dissociates from growth factor receptor complexes and increases its interaction with the small GTPase Rab5. This p110β-Rab5 association maintains Rab5 in its guanosine triphosphate (GTP)-bound state and enhances the Rab5-Vps34 interaction that promotes autophagy. p110β mutants that fail to interact with Rab5 are defective in autophagy promotion. Hence, in mammalian cells, p110β acts as a molecular sensor for growth factor availability and induces autophagy by activating a Rab5-mediated signaling cascade.

UR - http://www.scopus.com/inward/record.url?scp=84876086849&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84876086849&partnerID=8YFLogxK

U2 - 10.1016/j.molcel.2013.01.022

DO - 10.1016/j.molcel.2013.01.022

M3 - Article

C2 - 23434372

AN - SCOPUS:84876086849

VL - 50

SP - 29

EP - 42

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 1

ER -