Restricted Redundancy

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Science  29 Aug 2008:
Vol. 321, Issue 5893, pp. 1135
DOI: 10.1126/science.321.5893.1135c

The serine-threonine protein phosphatase PP2A, which participates in signaling cascades induced by TGF-β family ligands, is a heterotrimer composed of catalytic, structural, and regulatory subunits. The B family of regulatory subunits comprises four members that differ in tissue specificity and subcellular localization but otherwise appear similar enough to be functionally redundant. Batut et al. report that Bα and Bδ have distinct functions in mediating signaling elicited by the ligands TGF-β, Activin, and Nodal. Bδ knockdown expanded anterior structures in Xenopus embryos, whereas Bα knockdown caused loss of anterior structures, suggesting that Bα potentiated and Bδ inhibited Nodal signaling. In Xenopus animal cap assays, Bα knockdown blocked Activin-induced axial elongation reduced phosphorylation of the TGF-β family effector Smad2 (pSmad2), and prevented nuclear accumulation of pSmad2. In contrast, Bδ knockdown enhanced elongation and increased the amount and nuclear accumulation of pSmad2, suggesting that Bα and Bδ affected Activin signaling oppositely. Knockdown analyses in keratinocytes and in Xenopus animal caps indicated that Bα inhibits lysosomal degradation of ALK4 and ALK5—type I receptors that transduce signaling from TGF-β ligands—and that Bδ inhibits ALK4 receptor clustering. Thus, both subunits appear to influence the threshold ligand concentration that can elicit signaling, but act on distinct processes to exert their opposing effects. — AMV

Development 135, 2927 (2008).

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