PMID- 23861542
OWN - NLM
STAT- MEDLINE
DCOM- 20140204
LR  - 20211021
IS  - 1937-9145 (Electronic)
IS  - 1945-0877 (Linking)
VI  - 6
IP  - 284
DP  - 2013 Jul 16
TI  - Release of nonmuscle myosin II from the cytosolic domain of tumor necrosis factor 
      receptor 2 is required for target gene expression.
PG  - ra60
LID - 10.1126/scisignal.2003743 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) elicits its biological activities through 
      activation of TNF receptor 1 (TNFR1, also known as p55) and TNFR2 (also known as 
      p75). The activities of both receptors are required for the TNF-alpha-induced 
      proinflammatory response. The adaptor protein TNFR-associated factor 2 (TRAF2) is 
      critical for either p55- or p75-mediated activation of nuclear factor kappaB (NF-kappaB) 
      and mitogen-activated protein kinase (MAPK) signaling, as well as for target gene 
      expression. We identified nonmuscle myosin II (myosin) as a binding partner of 
      p75. TNF-alpha-dependent signaling by p75 and induction of target gene expression 
      persisted substantially longer in cells deficient in myosin regulatory light 
      chain (MRLC; a component of myosin) than in cells replete in myosin. In resting 
      endothelial cells, myosin was bound constitutively to the intracellular region of 
      p75, a region that overlaps with the TRAF2-binding domain, and TNF-alpha caused the 
      rapid dissociation of myosin from p75. At early time points after exposure to 
      TNF-alpha, p75 activated Rho-associated kinase 1 (ROCK1). Inhibition of ROCK1 
      activity blocked TNF-alpha-dependent phosphorylation of MRLC and the dissociation of 
      myosin from p75. ROCK1-dependent release of myosin was necessary for the 
      TNF-alpha-dependent recruitment of TRAF2 to p75 and for p75-specific activation of 
      NF-kappaB and MAPK signaling. Thus, our findings have revealed a previously 
      uncharacterized, noncanonical regulatory function of myosin in cytokine 
      signaling.
FAU - Chandrasekharan, Unni M
AU  - Chandrasekharan UM
AD  - Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research 
      Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
FAU - Dechert, Lisa
AU  - Dechert L
FAU - Davidson, Uchechukwu I
AU  - Davidson UI
FAU - Waitkus, Matthew
AU  - Waitkus M
FAU - Mavrakis, Lori
AU  - Mavrakis L
FAU - Lyons, Katherine
AU  - Lyons K
FAU - Beach, Jordan R
AU  - Beach JR
FAU - Li, Xiaoxia
AU  - Li X
FAU - Egelhoff, Thomas T
AU  - Egelhoff TT
FAU - Fox, Paul L
AU  - Fox PL
FAU - DiCorleto, Paul E
AU  - DiCorleto PE
LA  - eng
GR  - R01 GM050009/GM/NIGMS NIH HHS/United States
GR  - UL1 TR000439/TR/NCATS NIH HHS/United States
GR  - UL1TR000439/TR/NCATS NIH HHS/United States
GR  - P01 HL029582/HL/NHLBI NIH HHS/United States
GR  - HL29582/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130716
PL  - United States
TA  - Sci Signal
JT  - Science signaling
JID - 101465400
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type II)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.1 (ROCK2 protein, human)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
RN  - EC 3.6.1.- (Myosin Type II)
SB  - IM
MH  - Cytosol/*metabolism
MH  - Gene Expression Regulation/*physiology
MH  - Human Umbilical Vein Endothelial Cells/cytology/*metabolism
MH  - Humans
MH  - MAP Kinase Signaling System/*physiology
MH  - Myosin Type II/genetics/*metabolism
MH  - NF-kappa B/genetics/metabolism
MH  - Receptors, Tumor Necrosis Factor, Type I/genetics/metabolism
MH  - Receptors, Tumor Necrosis Factor, Type II/genetics/*metabolism
MH  - TNF Receptor-Associated Factor 2/genetics/metabolism
MH  - Tumor Necrosis Factor-alpha/genetics/metabolism
MH  - rho-Associated Kinases/genetics/metabolism
PMC - PMC3837481
MID - NIHMS524745
EDAT- 2013/07/19 06:00
MHDA- 2014/02/05 06:00
PMCR- 2014/01/16
CRDT- 2013/07/18 06:00
PHST- 2013/07/18 06:00 [entrez]
PHST- 2013/07/19 06:00 [pubmed]
PHST- 2014/02/05 06:00 [medline]
PHST- 2014/01/16 00:00 [pmc-release]
AID - 6/284/ra60 [pii]
AID - 10.1126/scisignal.2003743 [doi]
PST - epublish
SO  - Sci Signal. 2013 Jul 16;6(284):ra60. doi: 10.1126/scisignal.2003743.