Transforming growth factor-β1 inhibits type I inositol 1,4,5- trisphosphate receptor expression and enhances its phosphorylation in mesangial cells

Kumar Sharma, Lewei Wang, Yanqing Zhu, Shaila Bokkala, Suresh K. Joseph

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

A potentially important cross-talk characteristic of transforming growth factor-β (TGF-β) is to inhibit platelet-derived growth factor-induced intracellular calcium rise (Baffy, G., Sharma, K., Shi, W., Ziyadeh, F. N., and Williamson, J. R. (1995) Biochem. Biophys. Res. Commun. 210, 378-383) in murine mesangial cells. The present study examined the possible basis for this effect by evaluating the regulation of the type I inositol 1,4,5- trisphosphate receptor (IP3R) by TGF-β. TGF-β1 down-regulates IP3R protein expression by >90% with maximal and half-maximal effects after 8 and 2 h, respectively. TGF-β1 also decreased IP3R mRNA expression by 59% after 1 h. Phosphorylation of the IP3R was also demonstrated as early as 15 min after TGF-β1 exposure. Back phosphorylation assays of IP3R from TGF-β1- treated mesangial cells with protein kinase A (PKA), indicated that TGF-β1- induced phosphorylation of the IP3R occurs at similar sites as for PKA. In vitro kinase assays using the known IP3R peptide substrates for PKA, RPS- GRRESLTSFGNP and ARRDSVLAAS, demonstrated that TGF-β1 induces phosphorylation of both peptides (158 and 123% of control values, respectively). TGF-β1-induced phosphorylation was prevented by the addition of the PKA inhibitor peptide in the in vitro kinase assay. It is proposed that TGF-β-mediated effects on the IP3R may be an important characteristic of its ability to modulate the response of cells to factors that employ IP3R-mediated calcium release.

Original languageEnglish (US)
Pages (from-to)14617-14623
Number of pages7
JournalJournal of Biological Chemistry
Volume272
Issue number23
DOIs
StatePublished - Jun 6 1997
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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