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Activin A Induces Neuronal Differentiation and Survival via ALK4 in a SMAD-independent Manner in a Subpopulation of Human Neuroblastomas

Activin A Induces Neuronal Differentiation and Survival via ALK4 in a SMAD-independent Manner in a Subpopulation of Human Neuroblastomas

Kotaro Suzuki, Tomomi Kobayashi, Osamu Funatsu, Akinori Morita, Masahiko Ikekita

Biochem Biophys Res Commun. 2010 Apr 9;394(3):639-45.

PMID: 20226172

Abstract:

Activin A is a multifunctional homo-dimeric protein that belongs to the transforming growth factor (TGF)-beta superfamily. In neurons, activin has neuroprotective effects both in vitro and in vivo, but it inhibits neuronal differentiation in some cell lines. Here we report that activin A can promote neuronal differentiation in particular cases. We examined activin A-induced neuronal differentiation and survival in a selected subpopulation of a human neuroblastoma cell line, SK-N-SH, grown in low-serum (differentiation-inducing) conditions. Activin A caused dramatic neurite outgrowth, and increased the expression of neuronal markers and the transactivation of dopamine beta-hydroxylase. We demonstrated that the activin A signal is transduced through the activin A type 1 receptor, ALK4, and transactivates several TGF-beta target genes in a SMAD-independent manner. That is, activin A did not induce the phosphorylation of SMAD2/3, the interaction of SMAD2/3 with SMAD4, the binding of SMAD2/3 to the promoter of TGF-beta target genes, or the accumulation of SMAD2/3 in the nucleus. These results suggest that, in particular cases, activin A can induce neuronal differentiation and support neuronal survival in vitro. These findings may reflect previously unknown functions of activin A in neuronal cells in vivo.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248740	Activin A human			Price

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