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Inhibition of H-Ras and MAPK is compensated by PKC-dependent pathways in annexin A6 expressing cells

Carles Rentero1, Rachael Evans, Peta Wood

  • 1Departament de Biologia Cellular, Facultat de Medicina, Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, and Centre for Immunology, St. Vincent's Hospital, Sydney, NSW, Australia.

Cellular Signalling
|September 27, 2005
PubMed

Insights

High-density lipoprotein (HDL) activates the Ras/MAPK pathway. In cells expressing annexin A6, HDL-induced H-Ras and MAPK activation becomes protein kinase C (PKC)-dependent, compensating for reduced PKC-independent pathways.

Area of Science:

  • Cellular signaling pathways
  • Lipid metabolism and cell communication

Background:

  • High-density lipoprotein (HDL) signaling involves the Ras/MAPK pathway, mediated by both protein kinase C (PKC)-dependent and independent mechanisms.
  • HDL binding to scavenger receptor BI (SR-BI) in Chinese hamster ovary (CHO) cells typically activates Ras and MAPK via a PKC-independent route.
  • Annexin A6 expression in CHO cells (CHOanx6) reduces HDL-induced Ras and Raf-1 activation.

Purpose of the Study:

  • To investigate the role of protein kinase C (PKC) in HDL-induced Ras and MAPK activation in annexin A6-expressing CHO cells (CHOanx6).
  • To elucidate the compensatory mechanisms for reduced PKC-independent signaling in CHOanx6 cells.

Main Methods:

  • Utilized CHO and CHOanx6 cell lines.
  • Investigated HDL-induced activation of the Ras/MAPK pathway.
  • Assessed the involvement of PKCalpha in HDL signaling.

Main Results:

  • HDL binding to SR-BI in CHO cells activates Ras and MAPK independently of PKC.
  • HDL-induced Ras and Raf-1 activation is diminished in CHOanx6 cells.
  • Despite reduced Ras and Raf-1 activity, HDL still induces MAPK phosphorylation in CHOanx6 cells.
  • HDL-induced H-Ras and MAPK activation is PKC-dependent in CHOanx6 cells.

Conclusions:

  • Annexin A6 expression shifts HDL-induced H-Ras and MAPK activation towards a PKC-dependent pathway.
  • This PKC-dependent activation compensates for the loss of PKC-independent signaling in annexin A6-expressing cells.
  • The findings highlight a novel regulatory mechanism in HDL signaling involving annexin A6 and PKC.

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