Myristoylated alanine-rich protein kinase c substrate (MARCKS) has been suggested to be implicated in cell adhesion, secretion, motility and mitogenesis through regulation of the actin cytoskeletal structure. In the present study, a possible link between MARCKS and the platelet-derived growth factor (PDGF) signaling pathway was investigated in activated human hepatic stellate cells (hHSC), critical regulators of hepatic fibrogenesis. PDGF-BB stimulation resulted in a bi-directional movement of MARCKS that coincided with the phosphorylation of MARCKS and the activation of both PKCepsilon and PKCalpha. Biochemical inhibition of PKC kinase activity and small interfering RNA (siRNA) against PKCepsilon demonstrated that PKCepsilon is indispensable for PDGF-BB-induced MARCKS phosphorylation and cell migration. Immunoprecipitation studies revealed an association between MARCKS and the PDGFbeta-receptor, while the PDGFbeta-receptor and PKCalpha associated with focal adhesion kinase (FAK). Transient transfection with MARCKS DNA plasmid remarkably reduced PDGF-BB stimulated cell motility. In contrast, siRNA against MARCKS increased cell migration in RNAi treated cells in comparison to the scrambled control cells. In conclusion, the present study indicates that MARCKS play a major key role in PDGF-BB-induced chemotaxis in activated hHSC.

MARCKS is a downstream effector in platelet-derived growth factor-induced cell motility in activated human hepatic stellate cells / K. Rombouts; B. Lottini; A. Caligiuri; F. Liotta; T. Mello; V. Carloni; F. Marra; M. Pinzani. - In: EXPERIMENTAL CELL RESEARCH. - ISSN 0014-4827. - STAMPA. - 314:(2008), pp. 1444-1454.

MARCKS is a downstream effector in platelet-derived growth factor-induced cell motility in activated human hepatic stellate cells

ROMBOUTS, KRISTA LOUISA PIETER;LOTTINI, BENEDETTA;CALIGIURI, ALESSANDRA;LIOTTA, FRANCESCO;MELLO, TOMMASO;CARLONI, VINICIO;MARRA, FABIO;PINZANI, MASSIMO
2008

Abstract

Myristoylated alanine-rich protein kinase c substrate (MARCKS) has been suggested to be implicated in cell adhesion, secretion, motility and mitogenesis through regulation of the actin cytoskeletal structure. In the present study, a possible link between MARCKS and the platelet-derived growth factor (PDGF) signaling pathway was investigated in activated human hepatic stellate cells (hHSC), critical regulators of hepatic fibrogenesis. PDGF-BB stimulation resulted in a bi-directional movement of MARCKS that coincided with the phosphorylation of MARCKS and the activation of both PKCepsilon and PKCalpha. Biochemical inhibition of PKC kinase activity and small interfering RNA (siRNA) against PKCepsilon demonstrated that PKCepsilon is indispensable for PDGF-BB-induced MARCKS phosphorylation and cell migration. Immunoprecipitation studies revealed an association between MARCKS and the PDGFbeta-receptor, while the PDGFbeta-receptor and PKCalpha associated with focal adhesion kinase (FAK). Transient transfection with MARCKS DNA plasmid remarkably reduced PDGF-BB stimulated cell motility. In contrast, siRNA against MARCKS increased cell migration in RNAi treated cells in comparison to the scrambled control cells. In conclusion, the present study indicates that MARCKS play a major key role in PDGF-BB-induced chemotaxis in activated hHSC.
2008
314
1444
1454
Goal 3: Good health and well-being
K. Rombouts; B. Lottini; A. Caligiuri; F. Liotta; T. Mello; V. Carloni; F. Marra; M. Pinzani
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/325237
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