Requirement of a dynein light chain in TGFβ/Smad3 signaling

Qunyan Jin, Guofeng Gao, Kathleen M. Mulder

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

We have previously reported that the dynein light chain (DLC) km23-1 is required for Smad2-dependent TGFβ signaling. Here we describe another member of the km23/DYNLRB/LC7/robl family of DLCs, termed km23-2, which is also involved in TGFβ signaling. We show not only that TGFβ stimulates the interaction of km23-2 (DYNLRB2) with TGFβ receptor II (TβRII) but also that TGFβ regulates the interaction between km23-2 and endogenous TβRII in vivo. In addition, TGFβ treatment causes km23-2 phosphorylation, whereas a kinase-deficient form of TβRII prevents km23-2 phosphorylation. In contrast to the km23-1 isoform, blockade of km23-2 expression using small interfering RNAs (siRNAs) decreased key TGFβ/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 TGFβ/ Smad3 responses under similar conditions. Further, km23-2 was required for TGFβ stimulation of Smad3-dependent Smad-binding element (SBE)2-Luc transcriptional activity, but not for TGFβ 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 TGFβ responses, immunoprecipitation (IP)/blot analyses were performed, which demonstrate that TGFβ stimulated preferential complex formation of km23-2 with Smad3, relative to Smad2. Collectively, our findings indicate that km23-2 is required for Smad3-dependent TGFβ signaling. More importantly, we demonstrate that km23-2 has functions in TGFβ 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 TGFβ signaling.

Original languageEnglish (US)
Pages (from-to)707-715
Number of pages9
JournalJournal of Cellular Physiology
Volume221
Issue number3
DOIs
StatePublished - Dec 2009

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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