Phosphorylation of transcriptional coactivator peroxisome proliferator-activated receptor (PPAR)-binding protein (PBP). Stimulation of transcriptional regulation by mitogen-activated protein kinase

Parimal Misra, Edward D. Owuor, Wenge Li, Songtao Yu, Chao Qi, Kirstin Meyer, Yi Jun Zhu, M. Sambasiva Rao, A. N Tony Kong, Janardan K. Reddy

Research output: Contribution to journalArticle

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Abstract

Peroxisome proliferator-activated receptor (PPAR)-binding protein (PBP) is an important coactivator for PPARγ and other transcription factors. PBP is an integral component of a maltiprotein thyroid hormone receptor-associated protein (TRAP)/vitamin D3 receptor-interacting protein (DRIP)/activator-recruited cofactor (ARC) complex required for transcriptional activity. To study the regulation of PBP by cellular signaling pathways, we identified the phosphorylation sites of PBP. Using a combination of in vitro and in vivo approaches and mutagenesis of PBP phosphorylation sites, we identified six phosphorylation sites on PBP: one exclusive protein kinase A (PKA) phosphorylation site at serine 656, two protein kinase C (PKC) sites at serine 796 and serine 1345, a common PKA/PKC site at serine 756, and two extracellular signal-regulated kinase 2 sites of the mitogen-activated protein kinase (MAPK) family at threonine 1017 and threonine 1444. Binding of PBP to PPARγ1 or retinoid-X-receptor for 9-cis-retinoic acid (RXR) is independent of their phosphorylation states, implying no changes in protein-protein interaction after modification by phosphorylation. Overexpression of RafBXB, an activated upstream kinase of the MAPK signal transduction pathway, exerts a significant additive inductive effect on PBP coactivator function. This effect is significantly diminished by overexpression of Raf-BXB301, a dominant negative mutant of RafBXB. These results identify phosphorylation as a regulatory modification event of PBP and demonstrate that PBP phosphorylation by Raf/MEK/MAPK cascade exerts a positive effect on PBP coactivator function. The functional role of PKA and PKC phosphorylation sites in PBP remains to be elucidated.

Original languageEnglish (US)
Pages (from-to)48745-48754
Number of pages10
JournalJournal of Biological Chemistry
Volume277
Issue number50
DOIs
StatePublished - Dec 13 2002
Externally publishedYes

Fingerprint

Mediator Complex Subunit 1
Phosphorylation
Mitogen-Activated Protein Kinases
Serine
Cyclic AMP-Dependent Protein Kinases
Protein Kinase C
Threonine
Receptor-Interacting Protein Serine-Threonine Kinases
Cell signaling
Retinoid X Receptors
Thyroid Hormone Receptors
Signal transduction
Mutagenesis
Calcitriol Receptors
Peroxisome Proliferator-Activated Receptors
Proteins
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase Kinases

ASJC Scopus subject areas

  • Biochemistry

Cite this

Phosphorylation of transcriptional coactivator peroxisome proliferator-activated receptor (PPAR)-binding protein (PBP). Stimulation of transcriptional regulation by mitogen-activated protein kinase. / Misra, Parimal; Owuor, Edward D.; Li, Wenge; Yu, Songtao; Qi, Chao; Meyer, Kirstin; Zhu, Yi Jun; Rao, M. Sambasiva; Kong, A. N Tony; Reddy, Janardan K.

In: Journal of Biological Chemistry, Vol. 277, No. 50, 13.12.2002, p. 48745-48754.

Research output: Contribution to journalArticle

Misra, Parimal ; Owuor, Edward D. ; Li, Wenge ; Yu, Songtao ; Qi, Chao ; Meyer, Kirstin ; Zhu, Yi Jun ; Rao, M. Sambasiva ; Kong, A. N Tony ; Reddy, Janardan K. / Phosphorylation of transcriptional coactivator peroxisome proliferator-activated receptor (PPAR)-binding protein (PBP). Stimulation of transcriptional regulation by mitogen-activated protein kinase. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 50. pp. 48745-48754.
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abstract = "Peroxisome proliferator-activated receptor (PPAR)-binding protein (PBP) is an important coactivator for PPARγ and other transcription factors. PBP is an integral component of a maltiprotein thyroid hormone receptor-associated protein (TRAP)/vitamin D3 receptor-interacting protein (DRIP)/activator-recruited cofactor (ARC) complex required for transcriptional activity. To study the regulation of PBP by cellular signaling pathways, we identified the phosphorylation sites of PBP. Using a combination of in vitro and in vivo approaches and mutagenesis of PBP phosphorylation sites, we identified six phosphorylation sites on PBP: one exclusive protein kinase A (PKA) phosphorylation site at serine 656, two protein kinase C (PKC) sites at serine 796 and serine 1345, a common PKA/PKC site at serine 756, and two extracellular signal-regulated kinase 2 sites of the mitogen-activated protein kinase (MAPK) family at threonine 1017 and threonine 1444. Binding of PBP to PPARγ1 or retinoid-X-receptor for 9-cis-retinoic acid (RXR) is independent of their phosphorylation states, implying no changes in protein-protein interaction after modification by phosphorylation. Overexpression of RafBXB, an activated upstream kinase of the MAPK signal transduction pathway, exerts a significant additive inductive effect on PBP coactivator function. This effect is significantly diminished by overexpression of Raf-BXB301, a dominant negative mutant of RafBXB. These results identify phosphorylation as a regulatory modification event of PBP and demonstrate that PBP phosphorylation by Raf/MEK/MAPK cascade exerts a positive effect on PBP coactivator function. The functional role of PKA and PKC phosphorylation sites in PBP remains to be elucidated.",
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T1 - Phosphorylation of transcriptional coactivator peroxisome proliferator-activated receptor (PPAR)-binding protein (PBP). Stimulation of transcriptional regulation by mitogen-activated protein kinase

AU - Misra, Parimal

AU - Owuor, Edward D.

AU - Li, Wenge

AU - Yu, Songtao

AU - Qi, Chao

AU - Meyer, Kirstin

AU - Zhu, Yi Jun

AU - Rao, M. Sambasiva

AU - Kong, A. N Tony

AU - Reddy, Janardan K.

PY - 2002/12/13

Y1 - 2002/12/13

N2 - Peroxisome proliferator-activated receptor (PPAR)-binding protein (PBP) is an important coactivator for PPARγ and other transcription factors. PBP is an integral component of a maltiprotein thyroid hormone receptor-associated protein (TRAP)/vitamin D3 receptor-interacting protein (DRIP)/activator-recruited cofactor (ARC) complex required for transcriptional activity. To study the regulation of PBP by cellular signaling pathways, we identified the phosphorylation sites of PBP. Using a combination of in vitro and in vivo approaches and mutagenesis of PBP phosphorylation sites, we identified six phosphorylation sites on PBP: one exclusive protein kinase A (PKA) phosphorylation site at serine 656, two protein kinase C (PKC) sites at serine 796 and serine 1345, a common PKA/PKC site at serine 756, and two extracellular signal-regulated kinase 2 sites of the mitogen-activated protein kinase (MAPK) family at threonine 1017 and threonine 1444. Binding of PBP to PPARγ1 or retinoid-X-receptor for 9-cis-retinoic acid (RXR) is independent of their phosphorylation states, implying no changes in protein-protein interaction after modification by phosphorylation. Overexpression of RafBXB, an activated upstream kinase of the MAPK signal transduction pathway, exerts a significant additive inductive effect on PBP coactivator function. This effect is significantly diminished by overexpression of Raf-BXB301, a dominant negative mutant of RafBXB. These results identify phosphorylation as a regulatory modification event of PBP and demonstrate that PBP phosphorylation by Raf/MEK/MAPK cascade exerts a positive effect on PBP coactivator function. The functional role of PKA and PKC phosphorylation sites in PBP remains to be elucidated.

AB - Peroxisome proliferator-activated receptor (PPAR)-binding protein (PBP) is an important coactivator for PPARγ and other transcription factors. PBP is an integral component of a maltiprotein thyroid hormone receptor-associated protein (TRAP)/vitamin D3 receptor-interacting protein (DRIP)/activator-recruited cofactor (ARC) complex required for transcriptional activity. To study the regulation of PBP by cellular signaling pathways, we identified the phosphorylation sites of PBP. Using a combination of in vitro and in vivo approaches and mutagenesis of PBP phosphorylation sites, we identified six phosphorylation sites on PBP: one exclusive protein kinase A (PKA) phosphorylation site at serine 656, two protein kinase C (PKC) sites at serine 796 and serine 1345, a common PKA/PKC site at serine 756, and two extracellular signal-regulated kinase 2 sites of the mitogen-activated protein kinase (MAPK) family at threonine 1017 and threonine 1444. Binding of PBP to PPARγ1 or retinoid-X-receptor for 9-cis-retinoic acid (RXR) is independent of their phosphorylation states, implying no changes in protein-protein interaction after modification by phosphorylation. Overexpression of RafBXB, an activated upstream kinase of the MAPK signal transduction pathway, exerts a significant additive inductive effect on PBP coactivator function. This effect is significantly diminished by overexpression of Raf-BXB301, a dominant negative mutant of RafBXB. These results identify phosphorylation as a regulatory modification event of PBP and demonstrate that PBP phosphorylation by Raf/MEK/MAPK cascade exerts a positive effect on PBP coactivator function. The functional role of PKA and PKC phosphorylation sites in PBP remains to be elucidated.

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