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08:51
Induction of Adhesion-dependent Signals Using Low-intensity Ultrasound
Published on: May 8, 2012
Sequences within fibrinogen and intercellular adhesion molecule-1 (ICAM-1) modulate signals required for mitogenesis
1Joseph J. Jacobs Center for Thrombosis and Vascular Biology, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
The Journal of Biological Chemistry
|April 17, 1999
Summary
Fibrinogen binding to ICAM-1 on B-cells triggers cell growth via tyrosine kinases and ERK-1 signaling. Specific peptide sequences in fibrinogen and ICAM-1 are crucial for this mitogenic process.
Area of Science:
- Cellular Biology
- Immunology
- Biochemistry
Background:
- Fibrinogen (Fg) interaction with intercellular adhesion molecule-1 (ICAM) on B-lymphoid Raji cells induces mitogenesis.
- Previous studies indicated ICAM-1-(8-22) blocks Fg-induced mitogenesis, while Fg-gamma-(117-133) peptide induces proliferation.
Purpose of the Study:
- To investigate the signaling pathways involved in Fg-ICAM-1-mediated B-cell proliferation.
- To determine the role of tyrosine kinases and ERK-1 in this cellular response.
Main Methods:
- Raji cells were incubated with Fg, and tyrosine phosphorylation of pp60(Src) and ERK-1 was assessed.
- Peptide inhibitors (ICAM-1-(8-22), Fg-gamma-(117-133)) and specific kinase inhibitors (PD98059, geldanamycin, herbimycin A) were used.
- Cell proliferation and kinase enzymatic activity were measured.
Main Results:
- Fg increased tyrosine phosphorylation of pp60(Src) and ERK-1.
- ICAM-1-(8-22) peptide blocked ERK-1 phosphorylation and activity, while Fg-gamma-(117-133) increased ERK-1 phosphorylation.
- MEK inhibitor PD98059 and pp60(Src) inhibitors geldanamycin/herbimycin A significantly blocked Raji cell proliferation.
Conclusions:
- Fg-ICAM-1-induced B-cell proliferation is partly mediated by receptor-associated tyrosine kinases and ERK-1 signaling.
- Specific recognition sequences within Fg and ICAM-1 play a role in initiating this signaling cascade.
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