PMID- 20961289
OWN - NLM
STAT- MEDLINE
DCOM- 20110210
LR  - 20211020
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Print)
IS  - 0264-6021 (Linking)
VI  - 433
IP  - 1
DP  - 2011 Jan 1
TI  - Contrasting effects of ERK on tight junction integrity in differentiated and 
      under-differentiated Caco-2 cell monolayers.
PG  - 51-63
LID - 10.1042/BJ20100249 [doi]
AB  - ERK (extracellular-signal-regulated kinase) activation leads to disruption of 
      tight junctions in some epithelial monolayers, whereas it prevents disruption of 
      tight junctions in other epithelia. The factors responsible for such contrasting 
      influences of ERK on tight junction integrity are unknown. The present study 
      investigated the effect of the state of cell differentiation on ERK-mediated 
      regulation of tight junctions in Caco-2 cell monolayers. EGF (epidermal growth 
      factor) potentiated H2O2-induced tight junction disruption in 
      under-differentiated cell monolayers, which was attenuated by the MEK [MAPK 
      (mitogen-activated protein kinase)/ERK kinase] inhibitor U0126. In contrast, EGF 
      prevented H2O2-induced disruption of tight junctions in differentiated cell 
      monolayers, which was also attenuated by U0126. Knockdown of ERK1/2 enhanced 
      tight junction integrity and accelerated assembly of tight junctions in 
      under-differentiated cell monolayers, whereas it had the opposite effect in 
      differentiated cell monolayers. Regulated expression of wild-type and 
      constitutively active MEK1 disrupted tight junctions, and the expression of 
      dominant-negative MEK1 enhanced tight junction integrity in under-differentiated 
      cells, whereas contrasting responses were recorded in differentiated cells. EGF 
      prevented both H2O2-induced association of PP2A (protein phosphatase 2A), and 
      loss of association of PKCzeta (protein kinase Czeta), with occludin by an 
      ERK-dependent mechanism in differentiated cell monolayers, but not in 
      under-differentiated cell monolayers. Active ERK was distributed in the 
      intracellular compartment in under-differentiated cell monolayers, whereas it was 
      localized mainly in the perijunctional region in differentiated cell monolayers. 
      Thus ERK may exhibit its contrasting influences on tight junction integrity in 
      under-differentiated and differentiated epithelial cells by virtue of differences 
      in its subcellular distribution and ability to regulate the association of PKCzeta 
      and PP2A with tight junction proteins.
FAU - Aggarwal, Sudhir
AU  - Aggarwal S
AD  - Department of Physiology, University of Tennessee Health Sciences Center, 
      Memphis, TN 38163, USA.
FAU - Suzuki, Takuya
AU  - Suzuki T
FAU - Taylor, William L
AU  - Taylor WL
FAU - Bhargava, Aditi
AU  - Bhargava A
FAU - Rao, Radhakrishna K
AU  - Rao RK
LA  - eng
GR  - R01 DK080787/DK/NIDDK NIH HHS/United States
GR  - R01-DK080787/DK/NIDDK NIH HHS/United States
GR  - R01 DK055532/DK/NIDDK NIH HHS/United States
GR  - R01-DK55532/DK/NIDDK NIH HHS/United States
GR  - R01-AA12307/AA/NIAAA NIH HHS/United States
GR  - R01 AA012307/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - EC 2.7.11.1 (protein kinase C zeta)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
RN  - EC 3.1.3.16 (Protein Phosphatase 2)
SB  - IM
MH  - Caco-2 Cells
MH  - Cell Differentiation/*physiology
MH  - Epithelial Cells/cytology/physiology
MH  - Extracellular Signal-Regulated MAP Kinases/analysis/*physiology
MH  - Humans
MH  - MAP Kinase Kinase 1/physiology
MH  - Protein Binding
MH  - Protein Kinase C/metabolism
MH  - Protein Phosphatase 2/metabolism
MH  - *Tight Junctions
MH  - Tissue Distribution
PMC - PMC4438673
MID - NIHMS453906
EDAT- 2010/10/22 06:00
MHDA- 2011/02/11 06:00
PMCR- 2015/05/20
CRDT- 2010/10/22 06:00
PHST- 2010/10/22 06:00 [entrez]
PHST- 2010/10/22 06:00 [pubmed]
PHST- 2011/02/11 06:00 [medline]
PHST- 2015/05/20 00:00 [pmc-release]
AID - BJ20100249 [pii]
AID - 10.1042/BJ20100249 [doi]
PST - ppublish
SO  - Biochem J. 2011 Jan 1;433(1):51-63. doi: 10.1042/BJ20100249.