cGMP-dependent protein kinase Iβ physically and functionally interacts with the transcriptional regulator TFII-I

Darren E. Casteel, Shunhui Zhuang, Tanima Gudi, Julian Tang, Milena Vuica, Stephen Desiderio, Renate B. Pilz

Research output: Contribution to journalArticlepeer-review

Abstract

Transcriptional regulation of the fos promoter by nitric oxide and cGMP can occur by nuclear translocation of cGMP-dependent protein kinase I (G-kinase I) (Gudi, T., Lohmann, S. M., and Pilz, R. B. (1997) Mol. Cell. Biol. 17, 5244-5254). To identify nuclear targets of G-kinase I, we performed a yeast two-hybrid screen with G-kinase Iβ as bait. We found that G-kinase Iβ interacted specifically with TFII-I, an unusual transcriptional regulator that associates with multiple proteins to modulate both basal and signal-induced transcription. By using purified recombinant proteins, the interaction was mapped to the N-terminal 93 amino acids of G-kinase Iβ and one of six 95-amino acid repeats found in TFII-I. In baby hamster kidney cells, cGMP analogs enhanced co-immunoprecipitation of G-kinase Iβ and TFII-I by inducing co-localization of both proteins in the nucleus, but in other cell types containing cytoplasmic TFII-I the G-kinase-TFII-I interaction was largely cGMP-independent. G-kinase phosphorylated TFII-I in vitro and in vivo on Ser371 and Ser743 outside of the interaction domain. G-kinase strongly enhanced TFII-I transactivation of a serum-response element-containing promoter in COS7 cells, and this effect was lost when Ser371 and Ser743 of TFII-I were mutated. TFII-I by itself had little effect on a full-length fos promoter in baby hamster kidney cells, but it synergistically enhanced transcriptional activation by G-kinase Iβ. Binding of G-kinase to TFII-I may position the kinase to phosphorylate and regulate TFII-I and/or factors that interact with TFII-I at the serumresponse element.

Original languageEnglish (US)
Pages (from-to)32003-32014
Number of pages12
JournalJournal of Biological Chemistry
Volume277
Issue number35
DOIs
StatePublished - Aug 30 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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