PMID- 16754954
OWN - NLM
STAT- MEDLINE
DCOM- 20060822
LR  - 20181113
IS  - 0021-9525 (Print)
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Linking)
VI  - 173
IP  - 5
DP  - 2006 Jun 5
TI  - Myosin motor Myo1c and its receptor NEMO/IKK-gamma promote TNF-alpha-induced 
      serine307 phosphorylation of IRS-1.
PG  - 665-71
AB  - Tumor necrosis factor-alpha (TNF-alpha) signaling through the IkappaB kinase 
      (IKK) complex attenuates insulin action via the phosphorylation of insulin 
      receptor substrate 1 (IRS-1) at Ser307. However, the precise molecular mechanism 
      by which the IKK complex phosphorylates IRS-1 is unknown. In this study, we 
      report nuclear factor kappaB essential modulator (NEMO)/IKK-gamma subunit 
      accumulation in membrane ruffles followed by an interaction with IRS-1. This 
      intracellular trafficking of NEMO requires insulin, an intact actin cytoskeletal 
      network, and the motor protein Myo1c. Increased Myo1c expression enhanced the 
      NEMO-IRS-1 interaction, which is essential for TNF-alpha- induced phosphorylation 
      of Ser307-IRS-1. In contrast, dominant inhibitory Myo1c cargo domain expression 
      diminished this interaction and inhibited IRS-1 phosphorylation. NEMO expression 
      also enhanced TNF-alpha-induced Ser307-IRS-1 phosphorylation and inhibited 
      glucose uptake. In contrast, a deletion mutant of NEMO lacking the 
      IKK-beta-binding domain or silencing NEMO blocked the TNF-alpha signal. Thus, 
      motor protein Myo1c and its receptor protein NEMO act cooperatively to form the 
      IKK-IRS-1 complex and function in TNF-alpha-induced insulin resistance.
FAU - Nakamori, Yoshitaka
AU  - Nakamori Y
AD  - Division of Molecular Analysis of Human Disorders, Department of Bio-Signal 
      Analysis, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan.
FAU - Emoto, Masahiro
AU  - Emoto M
FAU - Fukuda, Naofumi
AU  - Fukuda N
FAU - Taguchi, Akihiko
AU  - Taguchi A
FAU - Okuya, Shigeru
AU  - Okuya S
FAU - Tajiri, Michiko
AU  - Tajiri M
FAU - Miyagishi, Makoto
AU  - Miyagishi M
FAU - Taira, Kazunari
AU  - Taira K
FAU - Wada, Yoshinao
AU  - Wada Y
FAU - Tanizawa, Yukio
AU  - Tanizawa Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Insulin)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Irs1 protein, mouse)
RN  - 0 (Molecular Motor Proteins)
RN  - 0 (Myo1c protein, mouse)
RN  - 0 (NF-kappa B)
RN  - 0 (Phosphoproteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - EC 3.6.1.- (Myosin Type I)
RN  - EC 3.6.4.1 (Myosins)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Animals
MH  - Glucose/metabolism
MH  - I-kappa B Kinase/*metabolism
MH  - In Vitro Techniques
MH  - Insulin/pharmacology
MH  - Insulin Receptor Substrate Proteins
MH  - Mice
MH  - Molecular Motor Proteins
MH  - Myosin Type I
MH  - Myosins/*metabolism
MH  - NF-kappa B/drug effects/*metabolism
MH  - Phosphoproteins/*drug effects/metabolism
MH  - Phosphorylation
MH  - Protein Binding
MH  - Serine/biosynthesis/*drug effects
MH  - Signal Transduction/physiology
MH  - Tumor Necrosis Factor-alpha/pharmacology/*physiology
PMC - PMC2063884
EDAT- 2006/06/07 09:00
MHDA- 2006/08/23 09:00
PMCR- 2006/12/05
CRDT- 2006/06/07 09:00
PHST- 2006/06/07 09:00 [pubmed]
PHST- 2006/08/23 09:00 [medline]
PHST- 2006/06/07 09:00 [entrez]
PHST- 2006/12/05 00:00 [pmc-release]
AID - jcb.200601065 [pii]
AID - 200601065 [pii]
AID - 10.1083/jcb.200601065 [doi]
PST - ppublish
SO  - J Cell Biol. 2006 Jun 5;173(5):665-71. doi: 10.1083/jcb.200601065.