PMID- 16157472
OWN - NLM
STAT- MEDLINE
DCOM- 20060418
LR  - 20161124
IS  - 0898-6568 (Print)
IS  - 0898-6568 (Linking)
VI  - 18
IP  - 4
DP  - 2006 Apr
TI  - PI 3 kinase-dependent Akt kinase and PKCepsilon independently regulate 
      interferon-gamma-induced STAT1alpha serine phosphorylation to induce monocyte 
      chemotactic protein-1 expression.
PG  - 508-18
AB  - Monocyte chemotactic protein-1 (MCP-1) recruits activated phagocytes to the site 
      of tissue injury. Interferon-gamma (IFN-gamma) present in the microenvironment of 
      glomerulus acts on mesangial cells to induce local production of MCP-1. The 
      mechanism by which IFN-gamma stimulates expression of MCP-1 is not clear. We 
      therefore examined the role of PI 3 kinase signaling in regulating the 
      IFN-gamma-induced MCP-1 expression in mesangial cells. Blocking PI 3 kinase 
      activity with Ly294002 attenuated IFN-gamma-induced MCP-1 protein and mRNA 
      expression. IFN-gamma increased Akt kinase activity in a PI 3 kinase-dependent 
      manner. Expression of dominant negative Akt kinase inhibited serine 
      phosphorylation of STAT1alpha, without any effect on its tyrosine 
      phosphorylation, and decreased IFN-gamma-induced expression of MCP-1. These data 
      for the first time indicate a role for PI 3 kinase-dependent Akt kinase in MCP-1 
      expression. We have recently shown that along with Akt, PKCepsilon is a 
      downstream target of PI 3 kinase in IFN-gamma signaling. Similar to dominant 
      negative Akt kinase, dominant negative PKCepsilon also inhibited serine 
      phosphorylation of STAT1alpha without any effect on tyrosine phosphorylation. 
      Dominant negative PKCepsilon also abrogated MAPK activity, resulting in decrease 
      in IFN-gamma-induced MCP-1 expression. Furthermore, Akt and PKCepsilon are 
      present together in a signaling complex. IFN-gamma had no effect on this complex 
      formation, but did increase PKCepsilon-associated Akt kinase activity. PKCepsilon 
      did not regulate IFN-gamma-induced Akt kinase. Finally, expression of dominant 
      negative Akt kinase blocked IFN-gamma-stimulated MAPK activation. These data 
      provide the first evidence that PI 3 kinase-dependent Akt and PKCepsilon 
      activation independently regulate MAPK activity and serine phosphorylation of 
      STAT1alpha to increase expression of MCP-1.
FAU - Venkatesan, Balachandar A
AU  - Venkatesan BA
AD  - Department of Medicine, University of Texas Health Science Center, San Antonio, 
      TX 78220-3900, USA.
FAU - Mahimainathan, Lenin
AU  - Mahimainathan L
FAU - Ghosh-Choudhury, Nandini
AU  - Ghosh-Choudhury N
FAU - Gorin, Yves
AU  - Gorin Y
FAU - Bhandari, Basant
AU  - Bhandari B
FAU - Valente, Anthony J
AU  - Valente AJ
FAU - Abboud, Hanna E
AU  - Abboud HE
FAU - Choudhury, Goutam Ghosh
AU  - Choudhury GG
LA  - eng
GR  - P50 DK061597/DK/NIDDK NIH HHS/United States
GR  - R01 DK33665/DK/NIDDK NIH HHS/United States
GR  - R01 DK50190/DK/NIDDK NIH HHS/United States
GR  - R01 DK55815/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20050912
PL  - England
TA  - Cell Signal
JT  - Cellular signalling
JID - 8904683
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chromones)
RN  - 0 (Interferon-Stimulated Gene Factor 3)
RN  - 0 (Morpholines)
RN  - 0 (RNA, Messenger)
RN  - 0 (gamma interferon activation factor)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - 452VLY9402 (Serine)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.13 (Protein Kinase C-epsilon)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokine CCL2/drug effects/*genetics/metabolism
MH  - Chromones/pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Interferon-Stimulated Gene Factor 3/drug effects/*metabolism
MH  - Interferon-gamma/*pharmacology
MH  - Mesangial Cells/drug effects/metabolism
MH  - Morpholines/pharmacology
MH  - Phosphatidylinositol 3-Kinases/drug effects/*metabolism
MH  - Phosphorylation/drug effects
MH  - Protein Kinase C-epsilon/*metabolism
MH  - Proto-Oncogene Proteins c-akt/drug effects/*metabolism
MH  - RNA, Messenger/drug effects/genetics/metabolism
MH  - Rats
MH  - Serine/drug effects/metabolism
MH  - Signal Transduction/drug effects/physiology
EDAT- 2005/09/15 09:00
MHDA- 2006/04/19 09:00
CRDT- 2005/09/15 09:00
PHST- 2005/04/19 00:00 [received]
PHST- 2005/05/18 00:00 [revised]
PHST- 2005/05/24 00:00 [accepted]
PHST- 2005/09/15 09:00 [pubmed]
PHST- 2006/04/19 09:00 [medline]
PHST- 2005/09/15 09:00 [entrez]
AID - S0898-6568(05)00124-5 [pii]
AID - 10.1016/j.cellsig.2005.05.022 [doi]
PST - ppublish
SO  - Cell Signal. 2006 Apr;18(4):508-18. doi: 10.1016/j.cellsig.2005.05.022. Epub 2005 
      Sep 12.