JCB logo
Sign up for e-mail content alerts
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 21 March 2005. doi:10.1083/jcb.200407027
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 168, Number 7, 1077-1086
This Article
Right arrow Full Text
Right arrow PDF (Full Text)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by König, H.-G.
Right arrow Articles by Prehn, J. H.M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by König, H.-G.
Right arrow Articles by Prehn, J. H.M.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Article

 TGF-ß1 activates two distinct type I receptors in neurons : implications for neuronal NF-{kappa}B signaling



Hans-Georg König1, Donat Kögel1, Abdelhaq Rami2, and Jochen H.M. Prehn1,3

1 Experimental Neurosurgery, Center for Neurology and Neurosurgery
2 Department of Anatomy III, Johann Wolfgang Goethe-University Clinics, D-60590 Frankfurt, Germany
3 Department of Physiology, Neuroscience Research Centre, Royal College of Surgeons in Ireland, Dublin 2, Ireland

Correspondence to Jochen H.M. Prehn: prehn{at}rcsi.ie

Transforming growth factor-ßs (TGF-ßs) are pleiotropic cytokines involved in development and maintenance of the nervous system. In several neural lesion paradigms, TGF-ß1 exerts potent neuroprotective effects. Neurons treated with TGF-ß1 activated the canonical TGF-ß receptor I/activin-like kinase receptor 5 (ALK5) pathway. The transcription factor nuclear factor-{kappa}B (NF-{kappa}B) plays a fundamental role in neuroprotection. Treatment with TGF-ß1 enhanced NF-{kappa}B activity in gelshift and reporter gene analyses. However, ectopic expression of a constitutively active ALK5 failed to mimic these effects. ALK1 has been described as an alternative TGF-ß receptor in endothelial cells. Interestingly, we detected significant basal expression of ALK1 and its injury-induced up-regulation in neurons. Treatment with TGF-ß1 also induced a pronounced increase in downstream Smad1 phosphorylation. Overexpression of a constitutively active ALK1 mimicked the effect of TGF-ß1 on NF-{kappa}B activation and neuroprotection. Our data suggest that TGF-ß1 simultaneously activates two distinct receptor pathways in neurons and that the ALK1 pathway mediates TGF-ß1–induced NF-{kappa}B survival signaling.

Abbreviations used in this paper: ALK5, activin-like kinase 5; BMP, bone morphogenetic protein; DIV, days in vitro; GFAP, glial acidic fibrillary protein; MCAO, middle cerebral artery occlusion; NF-{kappa}B, nuclear factor-{kappa}B; NMDA, N-methyl-D-aspartate; NO, nitric oxide; PI, propidium iodide; SNOC, S-nitroso-cysteine; TßRI, TGF-ß receptor type I; TGF-ß, transforming growth factor-ß.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents