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Cell adhesion regulates platelet‐derived growth factor–induced MAP kinase and PI‐3 kinase activation in stellate cells
Author(s) -
Carloni Vinicio,
DeFranco Raffaella M. S.,
Caligiuri Alessandra,
Gentilini Alessandra,
Sciammetta Silvia Cappadona,
Baldi Elisabetta,
Lottini Benedetta,
Gentilini Paolo,
Pinzani Massimo
Publication year - 2002
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2002.35277
Subject(s) - platelet derived growth factor receptor , microbiology and biotechnology , focal adhesion , ptk2 , tyrosine phosphorylation , cell adhesion , platelet derived growth factor , proto oncogene tyrosine protein kinase src , protein kinase b , cell growth , phosphorylation , growth factor , tyrosine kinase , biology , signal transduction , cell , biochemistry , receptor
The biologic effects of growth factors are dependent on cell adhesion, and a cross talk occurs between growth factors and adhesion complexes. The aim of the present study was to evaluate the influence of cell adhesion on the major intracellular signaling pathways elicited by platelet‐derived growth factor (PDGF) in hepatic stellate cells (HSC). PDGF signaling was investigated in an experimental condition characterized by lack of cell adhesion for different intervals of time. Basal and PDGF‐induced focal adhesion kinase (FAK) tyrosine phosphorylation was maintained in a condition of cell suspension for 2, 4, and 6 hours, whereas it was completely lost after 12 and 24 hours. We examined MAP kinase activity at 2 and 24 hours, corresponding to the higher and lower levels of FAK phosphorylation. In these experiments, MAP kinase activity correlated with FAK phosphorylation. Stimulation with PDGF was able to cause Ras‐GTP loading only in adherent cells. The ability of PDGF to induce phosphatidylinositol 3‐kinase (PI 3‐K) activity was abrogated in cells maintained in suspension. The Ser473 phosphorylation of Akt was only marginally affected by the lack of cell adhesion. We then evaluated the association of FAK with c‐Src. This association was found to be cell adhesion dependent, and it did not appear to be dependent from phosphorylated FAK. These changes in PDGF‐induced intracellular signaling were associated with a remarkable reduction of PDGF‐proliferative potential in nonadherent cells, although no marked differences in the apoptotic rate were observed. In conclusion, these results suggest that cell adhesion differentially regulates major signaling pathways activated by PDGF in HSC.