PMID- 14665433
OWN - NLM
STAT- MEDLINE
DCOM- 20040420
LR  - 20171116
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 286
IP  - 4
DP  - 2004 Apr
TI  - Functional caveolae are a prerequisite for CD40 signaling in human renal proximal 
      tubule cells.
PG  - F711-9
AB  - The role of caveolae in CD40/CD154 activation of proinflammatory chemokines and 
      their potential role in renal inflammatory disease were explored in primary 
      cultures of human renal proximal tubule epithelial cells. With the use of a cell 
      fractionation assay, caveolin-1 (Cav-1), the defining structural protein of 
      caveolae, was detected exclusively in the cell membrane (detergent insoluble) 
      component of resting and CD40-activated cells. In the unstimulated condition, 
      CD40 was associated with Cav-1, and with activation of the receptor by its 
      cognate ligand CD154, CD40 disassociated from Cav-1. Other previously identified 
      components of the CD40 signaling pathway, namely, SAPK/JNK, p38, and ERK1/2 
      MAPKs, but not tumor necrosis factor receptor-associated factor 6 (TRAF-6), were 
      also present within caveolae and dissociated from this structure with ligation of 
      the CD40 receptor. Disruption of caveolae with filipin diminished CD40-mediated 
      MAPK activation and blunted downstream monocyte chemoattractant protein-1 (MCP-1) 
      and IL-8 production. Similarly, dislodgment of signaling proteins from their 
      scaffolding with a peptide targeted to the Cav-1 scaffolding domain (CSD) 
      resulted in blunted MAPK activation and augmented IL-8 and MCP-1 production. In 
      contrast, epidermal growth factor (EGF)-mediated tyrosine phosphorylation of the 
      EGF receptor and activation of ERK1/2 were not interrupted by the peptide. We 
      conclude that in human renal proximal tubule epithelial cells, CD40 and its 
      downstream MAPK signaling proteins are located in membrane rafts and that 
      disruption of caveolae or dislodgment of signaling proteins from the CSD 
      diminishes MAPK activation and IL-8 and MCP-1 production in these cells.
FAU - Li, Hongye
AU  - Li H
AD  - Division of Nephrology, Department of Medicine, School of Medicine,State 
      University of New York at Stony Brook, Stony Brook, New York 11794, USA.
FAU - Nord, Edward P
AU  - Nord EP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20031209
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (CAV1 protein, human)
RN  - 0 (CD40 Antigens)
RN  - 0 (Caveolin 1)
RN  - 0 (Caveolins)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-8)
RN  - 0 (Peptide Fragments)
SB  - IM
MH  - Amino Acid Sequence
MH  - CD40 Antigens/*metabolism
MH  - Caveolae/*physiology
MH  - Caveolin 1
MH  - Caveolins/chemistry/metabolism
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Humans
MH  - Interleukin-8/biosynthesis
MH  - Kidney Tubules, Proximal/*cytology/*physiology
MH  - MAP Kinase Signaling System/*physiology
MH  - Molecular Sequence Data
MH  - Peptide Fragments/chemistry/metabolism/pharmacology
EDAT- 2003/12/11 05:00
MHDA- 2004/04/21 05:00
CRDT- 2003/12/11 05:00
PHST- 2003/12/11 05:00 [pubmed]
PHST- 2004/04/21 05:00 [medline]
PHST- 2003/12/11 05:00 [entrez]
AID - 00308.2003 [pii]
AID - 10.1152/ajprenal.00308.2003 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2004 Apr;286(4):F711-9. doi: 
      10.1152/ajprenal.00308.2003. Epub 2003 Dec 9.