Document Detail


Lysophosphatidic acid modulates c-Met redistribution and hepatocyte growth factor/c-Met signaling in human bronchial epithelial cells through PKC delta and E-cadherin.
MedLine Citation:
PMID:  17689924     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Previously we demonstrated that ligation of lysophosphatidic acid (LPA) to G protein-coupled LPA receptors induces transactivation of receptor tyrosine kinases (RTKs), such as platelet-derived growth factor receptor beta (PDGF-Rbeta) and epidermal growth factor receptor (EGF-R), in primary cultures of human bronchial epithelial cells (HBEpCs). Here we examined the role of LPA on c-Met redistribution and modulation of hepatocyte growth factor (HGF)/c-Met pathways in HBEpCs. Treatment of HBEpCs with LPA-induced c-Met serine phosphorylation and redistribution to plasma membrane, while treatment with HGF-induced c-Met internalization. Pretreatment with LPA reversed HGF-induced c-Met internalization. Overexpression of dominant negative (Dn)-PKC delta or pretreatment with Rottlerin or Pertussis toxin (PTx) attenuated LPA-induced c-Met serine phosphorylation and redistribution. Co-immnuoprecipitation and immunocytochemistry showed that E-cadherin interacted with c-Met in HBEpCs. LPA treatment induced E-cadherin and c-Met complex redistribution to plasma membranes. Overexpression of Dn-PKC delta attenuated LPA-induced E-cadherin redistribution and E-cadherin siRNA attenuated LPA-induced c-Met redistribution to plasma membrane. Furthermore, pretreatment of LPA attenuated HGF-induced c-Met tyrosine phosphorylation and downstream signaling, such as Akt kinase phosphorylation and cell motility. These results demonstrate that LPA regulates c-Met function through PKC delta and E-cadherin in HBEpCs, suggesting an alternate function of the cross-talk between G-protein-coupled receptors (GPCRs) and RTKs in HBEpCs.
Authors:
Yutong Zhao; Donghong He; Randi Stern; Peter V Usatyuk; Ernst Wm Spannhake; Ravi Salgia; Viswanathan Natarajan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-07-13
Journal Detail:
Title:  Cellular signalling     Volume:  19     ISSN:  0898-6568     ISO Abbreviation:  Cell. Signal.     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-09-10     Completed Date:  2007-11-13     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  8904683     Medline TA:  Cell Signal     Country:  England    
Other Details:
Languages:  eng     Pagination:  2329-38     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Acetophenones / pharmacology
Benzopyrans / pharmacology
Bronchi / cytology,  drug effects,  enzymology
Cadherins / metabolism*
Cell Movement / drug effects
Cells, Cultured
Endocytosis / drug effects
Epithelial Cells / cytology,  drug effects,  enzymology*
GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
Hepatocyte Growth Factor / pharmacology*
Humans
Lysophospholipids / pharmacology*
Models, Biological
Phosphoserine / metabolism
Phosphotyrosine / metabolism
Protein Binding / drug effects
Protein Kinase C-delta / metabolism*
Protein Transport / drug effects
Proto-Oncogene Proteins c-met / metabolism*
RNA, Small Interfering / metabolism
Signal Transduction / drug effects*
Grant Support
ID/Acronym/Agency:
CA100750/CA/NCI NIH HHS; CA109640/CA/NCI NIH HHS; HL71152/HL/NHLBI NIH HHS; HL79396/HL/NHLBI NIH HHS; R01 CA100750/CA/NCI NIH HHS; R01 CA100750-02/CA/NCI NIH HHS; R01 HL071152/HL/NHLBI NIH HHS; R01 HL071152-04/HL/NHLBI NIH HHS; R01 HL079396/HL/NHLBI NIH HHS; R01 HL079396-02/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Acetophenones; 0/Benzopyrans; 0/Cadherins; 0/Lysophospholipids; 0/RNA, Small Interfering; 17885-08-4/Phosphoserine; 21820-51-9/Phosphotyrosine; 22002-87-5/lysophosphatidic acid; 67256-21-7/Hepatocyte Growth Factor; E29LP3ZMUH/rottlerin; EC 2.7.10.1/Proto-Oncogene Proteins c-met; EC 2.7.11.13/Protein Kinase C-delta; EC 3.6.5.1/GTP-Binding Protein alpha Subunits, Gi-Go
Comments/Corrections

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