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  • Title: TGF-{beta}1 activates two distinct type I receptors in neurons: implications for neuronal NF-{kappa}B signaling.
    Author: König HG, Kögel D, Rami A, Prehn JH.
    Journal: J Cell Biol; 2005 Mar 28; 168(7):1077-86. PubMed ID: 15781474.
    Abstract:
    Transforming growth factor-betas (TGF-betas) are pleiotropic cytokines involved in development and maintenance of the nervous system. In several neural lesion paradigms, TGF-beta1 exerts potent neuroprotective effects. Neurons treated with TGF-beta1 activated the canonical TGF-beta receptor I/activin-like kinase receptor 5 (ALK5) pathway. The transcription factor nuclear factor-kappaB (NF-kappaB) plays a fundamental role in neuroprotection. Treatment with TGF-beta1 enhanced NF-kappaB 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-beta receptor in endothelial cells. Interestingly, we detected significant basal expression of ALK1 and its injury-induced up-regulation in neurons. Treatment with TGF-beta1 also induced a pronounced increase in downstream Smad1 phosphorylation. Overexpression of a constitutively active ALK1 mimicked the effect of TGF-beta1 on NF-kappaB activation and neuroprotection. Our data suggest that TGF-beta1 simultaneously activates two distinct receptor pathways in neurons and that the ALK1 pathway mediates TGF-beta1-induced NF-kappaB survival signaling.
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