In silico investigation of ADAM12 effect on TGF-beta receptors trafficking. - Archive ouverte HAL Access content directly
Journal Articles BMC Research Notes Year : 2009

In silico investigation of ADAM12 effect on TGF-beta receptors trafficking.

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Abstract

BACKGROUND: The transforming growth factor beta is known to have pleiotropic effects, including differentiation, proliferation and apoptosis. However the underlying mechanisms remain poorly understood. The regulation and effect of TGF-beta signaling is complex and highly depends on specific protein context. In liver, we have recently showed that the disintegrin and metalloproteinase ADAM12 interacts with TGF-beta receptors and modulates their trafficking among membranes, a crucial point in TGF-beta signaling and development of fibrosis. The present study aims to better understand how ADAM12 impacts on TGF-beta receptors trafficking and TGF-beta signaling. FINDINGS: We extracted qualitative biological observations from experimental data and defined a family of models producing a behavior compatible with the presence of ADAM12. We computationally explored the properties of this family of models which allowed us to make novel predictions. We predict that ADAM12 increases TGF-beta receptors internalization rate between the cell surface and the endosomal membrane. It also appears that ADAM12 modifies TGF-beta signaling shape favoring a permanent response by removing the transient component observed under physiological conditions. CONCLUSION: In this work, confronting differential models with qualitative biological observations, we obtained predictions giving new insights into the role of ADAM12 in TGF-beta signaling and hepatic fibrosis process.
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inserm-00663589 , version 1 (27-01-2012)

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Jérémy Gruel, Michel Leborgne, Nolwenn Lemeur, Nathalie Théret. In silico investigation of ADAM12 effect on TGF-beta receptors trafficking.. BMC Research Notes, 2009, 2 (1), pp.193. ⟨10.1186/1756-0500-2-193⟩. ⟨inserm-00663589⟩
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