RGD Reference Report - TGF-{beta}1 activates two distinct type I receptors in neurons: implications for neuronal NF-{kappa}B signaling. - Rat Genome Database

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TGF-{beta}1 activates two distinct type I receptors in neurons: implications for neuronal NF-{kappa}B signaling.

Authors: Konig, HG  Kogel, D  Rami, A  Prehn, JH 
Citation: Konig HG, etal., J Cell Biol. 2005 Mar 28;168(7):1077-86. Epub 2005 Mar 21.
RGD ID: 1579751
Pubmed: PMID:15781474   (View Abstract at PubMed)
PMCID: PMC2171851   (View Article at PubMed Central)
DOI: DOI:10.1083/jcb.200407027   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
transient cerebral ischemia  ISOAcvrl1 (Rattus norvegicus)1579751; 1579751 RGD 
transient cerebral ischemia  IEP 1579751 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of NF-kappaB transcription factor activity  IDA 1579751 RGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cell surface  IDA 1579751 RGD 
dendrite  IDA 1579751 RGD 
neuronal cell body  IDA 1579751 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Acvrl1  (activin A receptor like type 1)
Tgfb1  (transforming growth factor, beta 1)

Genes (Mus musculus)
Acvrl1  (activin A receptor, type II-like 1)

Genes (Homo sapiens)
ACVRL1  (activin A receptor like type 1)


Additional Information