Recent advances in the regulation of the TOR pathway by insulin and nutrients

Joseph Avruch, Yen-Shou Lin, Xiaomeng Long, Sid Murthy, Sara Ortiz-Vega

Research output: Contribution to journalReview article

87 Citations (Scopus)

Abstract

Purpose of Review: The aim of this article is to summarize recent advances in the understanding of the regulation of the target of rapamycin (TOR), a protein kinase that is regulated independently by insulin, amino acids and energy sufficiency and which participates in the control of the component of protein synthesis responsible for cell growth. Recent findings: These have been found in two major areas: genetic studies in Drosophila followed by studies in mammalian systems have identified the components of the Tuberous Sclerosis protein complex, a heterodimer of the proteins Hamartin and Tuberin, as inhibitors of TOR signaling, and as the major targets by which the insulin/IGF-1 signal transduction pathway, through the protein kinase PKB, and the energy status of the cell, through the AMP-activated protein kinase, regulate the TOR signaling. In turn, the inhibitory action of the tuberous sclerosis protein complex has been shown to be mediated by its ability to deactivate the small, ras-like GTPase Rheb. A second advance has been achieved by the identification of the TOR-associated protein raptor, as an indispensable substrate binding subunit of the TOR complex, and as the site at which the inhibitory effects on TOR signaling of rapamycin and amino acid deficiency converge. Summary: These findings bring us closer to the understanding of how nutrients and insulin coordinate protein synthesis to regulate anabolic cell growth.

Original languageEnglish
Pages (from-to)67-72
Number of pages6
JournalCurrent Opinion in Clinical Nutrition and Metabolic Care
Volume8
Issue number1
DOIs
Publication statusPublished - 2005 Jan 1

Fingerprint

Sirolimus
Insulin
Food
TOR Serine-Threonine Kinases
Tuberous Sclerosis
Proteins
Protein Kinases
Raptors
Amino Acids
ras Proteins
AMP-Activated Protein Kinases
Growth
Insulin-Like Growth Factor I
Drosophila
Signal Transduction

Keywords

  • LST8
  • Raptor
  • Rheb
  • TOR
  • Tuberous sclerosis complex

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Recent advances in the regulation of the TOR pathway by insulin and nutrients. / Avruch, Joseph; Lin, Yen-Shou; Long, Xiaomeng; Murthy, Sid; Ortiz-Vega, Sara.

In: Current Opinion in Clinical Nutrition and Metabolic Care, Vol. 8, No. 1, 01.01.2005, p. 67-72.

Research output: Contribution to journalReview article

Avruch, Joseph ; Lin, Yen-Shou ; Long, Xiaomeng ; Murthy, Sid ; Ortiz-Vega, Sara. / Recent advances in the regulation of the TOR pathway by insulin and nutrients. In: Current Opinion in Clinical Nutrition and Metabolic Care. 2005 ; Vol. 8, No. 1. pp. 67-72.
@article{b71c45f405e14e4bbbd26b8a6ae0be0b,
title = "Recent advances in the regulation of the TOR pathway by insulin and nutrients",
abstract = "Purpose of Review: The aim of this article is to summarize recent advances in the understanding of the regulation of the target of rapamycin (TOR), a protein kinase that is regulated independently by insulin, amino acids and energy sufficiency and which participates in the control of the component of protein synthesis responsible for cell growth. Recent findings: These have been found in two major areas: genetic studies in Drosophila followed by studies in mammalian systems have identified the components of the Tuberous Sclerosis protein complex, a heterodimer of the proteins Hamartin and Tuberin, as inhibitors of TOR signaling, and as the major targets by which the insulin/IGF-1 signal transduction pathway, through the protein kinase PKB, and the energy status of the cell, through the AMP-activated protein kinase, regulate the TOR signaling. In turn, the inhibitory action of the tuberous sclerosis protein complex has been shown to be mediated by its ability to deactivate the small, ras-like GTPase Rheb. A second advance has been achieved by the identification of the TOR-associated protein raptor, as an indispensable substrate binding subunit of the TOR complex, and as the site at which the inhibitory effects on TOR signaling of rapamycin and amino acid deficiency converge. Summary: These findings bring us closer to the understanding of how nutrients and insulin coordinate protein synthesis to regulate anabolic cell growth.",
keywords = "LST8, Raptor, Rheb, TOR, Tuberous sclerosis complex",
author = "Joseph Avruch and Yen-Shou Lin and Xiaomeng Long and Sid Murthy and Sara Ortiz-Vega",
year = "2005",
month = "1",
day = "1",
doi = "10.1097/00075197-200501000-00010",
language = "English",
volume = "8",
pages = "67--72",
journal = "Current Opinion in Clinical Nutrition and Metabolic Care",
issn = "1363-1950",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Recent advances in the regulation of the TOR pathway by insulin and nutrients

AU - Avruch, Joseph

AU - Lin, Yen-Shou

AU - Long, Xiaomeng

AU - Murthy, Sid

AU - Ortiz-Vega, Sara

PY - 2005/1/1

Y1 - 2005/1/1

N2 - Purpose of Review: The aim of this article is to summarize recent advances in the understanding of the regulation of the target of rapamycin (TOR), a protein kinase that is regulated independently by insulin, amino acids and energy sufficiency and which participates in the control of the component of protein synthesis responsible for cell growth. Recent findings: These have been found in two major areas: genetic studies in Drosophila followed by studies in mammalian systems have identified the components of the Tuberous Sclerosis protein complex, a heterodimer of the proteins Hamartin and Tuberin, as inhibitors of TOR signaling, and as the major targets by which the insulin/IGF-1 signal transduction pathway, through the protein kinase PKB, and the energy status of the cell, through the AMP-activated protein kinase, regulate the TOR signaling. In turn, the inhibitory action of the tuberous sclerosis protein complex has been shown to be mediated by its ability to deactivate the small, ras-like GTPase Rheb. A second advance has been achieved by the identification of the TOR-associated protein raptor, as an indispensable substrate binding subunit of the TOR complex, and as the site at which the inhibitory effects on TOR signaling of rapamycin and amino acid deficiency converge. Summary: These findings bring us closer to the understanding of how nutrients and insulin coordinate protein synthesis to regulate anabolic cell growth.

AB - Purpose of Review: The aim of this article is to summarize recent advances in the understanding of the regulation of the target of rapamycin (TOR), a protein kinase that is regulated independently by insulin, amino acids and energy sufficiency and which participates in the control of the component of protein synthesis responsible for cell growth. Recent findings: These have been found in two major areas: genetic studies in Drosophila followed by studies in mammalian systems have identified the components of the Tuberous Sclerosis protein complex, a heterodimer of the proteins Hamartin and Tuberin, as inhibitors of TOR signaling, and as the major targets by which the insulin/IGF-1 signal transduction pathway, through the protein kinase PKB, and the energy status of the cell, through the AMP-activated protein kinase, regulate the TOR signaling. In turn, the inhibitory action of the tuberous sclerosis protein complex has been shown to be mediated by its ability to deactivate the small, ras-like GTPase Rheb. A second advance has been achieved by the identification of the TOR-associated protein raptor, as an indispensable substrate binding subunit of the TOR complex, and as the site at which the inhibitory effects on TOR signaling of rapamycin and amino acid deficiency converge. Summary: These findings bring us closer to the understanding of how nutrients and insulin coordinate protein synthesis to regulate anabolic cell growth.

KW - LST8

KW - Raptor

KW - Rheb

KW - TOR

KW - Tuberous sclerosis complex

UR - http://www.scopus.com/inward/record.url?scp=13444252523&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=13444252523&partnerID=8YFLogxK

U2 - 10.1097/00075197-200501000-00010

DO - 10.1097/00075197-200501000-00010

M3 - Review article

C2 - 15586002

AN - SCOPUS:13444252523

VL - 8

SP - 67

EP - 72

JO - Current Opinion in Clinical Nutrition and Metabolic Care

JF - Current Opinion in Clinical Nutrition and Metabolic Care

SN - 1363-1950

IS - 1

ER -