Requirement of a dynein light chain in TGFbeta/Smad3 signaling.
J Cell Physiol
; 221(3): 707-15, 2009 Dec.
Article
em En
| MEDLINE
| ID: mdl-19711352
ABSTRACT
We have previously reported that the dynein light chain (DLC) km23-1 is required for Smad2-dependent TGFbeta signaling. Here we describe another member of the km23/DYNLRB/LC7/robl family of DLCs, termed km23-2, which is also involved in TGFbeta signaling. We show not only that TGFbeta stimulates the interaction of km23-2 (DYNLRB2) with TGFbeta receptor II (TbetaRII) but also that TGFbeta regulates the interaction between km23-2 and endogenous TbetaRII in vivo. In addition, TGFbeta treatment causes km23-2 phosphorylation, whereas a kinase-deficient form of TbetaRII prevents km23-2 phosphorylation. In contrast to the km23-1 isoform, blockade of km23-2 expression using small interfering RNAs (siRNAs) decreased key TGFbeta/Smad3-specific responses, including the induction of both plasminogen activator inhibitor-1 (PAI-1) gene expression and p21 protein expression. Blockade of km23-1 expression had no effect on these two major TGFbeta/Smad3 responses under similar conditions. Further, km23-2 was required for TGFbeta stimulation of Smad3-dependent Smad-binding element (SBE)2-Luc transcriptional activity, but not for TGFbeta stimulation of Smad2-dependent activin responsive element (ARE)-Lux transcriptional activity. In order to assess the mechanisms underlying the preferential stimulation of Smad3- versus Smad2-specific TGFbeta responses, immunoprecipitation (IP)/blot analyses were performed, which demonstrate that TGFbeta stimulated preferential complex formation of km23-2 with Smad3, relative to Smad2. Collectively, our findings indicate that km23-2 is required for Smad3-dependent TGFbeta signaling. More importantly, we demonstrate that km23-2 has functions in TGFbeta signaling that are distinct from those for km23-1. This is the first report to describe a differential requirement for unique isoforms of a specific DLC family in Smad-specific TGFbeta signaling.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Fator de Crescimento Transformador beta
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Dineínas
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Proteína Smad3
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Proteínas de Neoplasias
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Cell Physiol
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos