Phosphorylation of protein phosphatase type-1 inhibitory proteins by integrin-linked kinase and cyclic nucleotide-dependent protein kinases

F. Erdődi, Eniko Kiss, Michael P. Walsh, Bjarki Stefansson, Jing Ti Deng, Masumi Eto, David L. Brautigan, David J. Hartshorne

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Protein phosphatases play key roles in cellular regulation and are subjected to control by protein inhibitors whose activity is in turn regulated by phosphorylation. Here we investigated the possible regulation of phosphorylation-dependent type-1 protein phosphatase (PP1) inhibitors, CPI-17, PHI-1, and KEPI, by various kinases. Protein kinases A (PKA) and G (PKG) phosphorylated CPI-17 at the inhibitory site (T38), but not PHI-1 (T57). Phosphorylated CPI-17 inhibited the activity of both the PP1 catalytic subunit (PP1c) and the myosin phosphatase holoenzyme (MPH) with IC50 values of 1-8nM. PKA predominantly phosphorylated a site distinct from the inhibitory T73 in KEPI, whereas PKG was ineffective. Integrin-linked kinase phosphorylated KEPI (T73) and this dramatically increased inhibition of PP1c (IC50=0.1nM) and MPH (IC50=8nM). These results suggest that the regulatory phosphorylation of CPI-17 and KEPI may involve distinct kinases and signaling pathways.

Original languageEnglish
Pages (from-to)382-387
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume306
Issue number2
DOIs
Publication statusPublished - Jun 27 2003

Fingerprint

Protein Phosphatase 1
Phosphorylation
Cyclic Nucleotides
Protein Kinases
Myosin-Light-Chain Phosphatase
Inhibitory Concentration 50
Holoenzymes
Cyclic AMP-Dependent Protein Kinases
Catalytic Domain
Proteins
Phosphotransferases
Cyclic GMP-Dependent Protein Kinases
Phosphoprotein Phosphatases
cyclopropapyrroloindole
integrin-linked kinase
phosphoprotein phosphatase inhibitor 1

Keywords

  • C-kinase-enhanced (potentiated) phosphatase inhibitors (CPI-17 and KEPI)
  • Myosin phosphatase
  • Protein kinase A
  • Protein kinase G

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Phosphorylation of protein phosphatase type-1 inhibitory proteins by integrin-linked kinase and cyclic nucleotide-dependent protein kinases. / Erdődi, F.; Kiss, Eniko; Walsh, Michael P.; Stefansson, Bjarki; Deng, Jing Ti; Eto, Masumi; Brautigan, David L.; Hartshorne, David J.

In: Biochemical and Biophysical Research Communications, Vol. 306, No. 2, 27.06.2003, p. 382-387.

Research output: Contribution to journalArticle

Erdődi, F. ; Kiss, Eniko ; Walsh, Michael P. ; Stefansson, Bjarki ; Deng, Jing Ti ; Eto, Masumi ; Brautigan, David L. ; Hartshorne, David J. / Phosphorylation of protein phosphatase type-1 inhibitory proteins by integrin-linked kinase and cyclic nucleotide-dependent protein kinases. In: Biochemical and Biophysical Research Communications. 2003 ; Vol. 306, No. 2. pp. 382-387.
@article{30d9069f10e04217b7bb50de48290e3a,
title = "Phosphorylation of protein phosphatase type-1 inhibitory proteins by integrin-linked kinase and cyclic nucleotide-dependent protein kinases",
abstract = "Protein phosphatases play key roles in cellular regulation and are subjected to control by protein inhibitors whose activity is in turn regulated by phosphorylation. Here we investigated the possible regulation of phosphorylation-dependent type-1 protein phosphatase (PP1) inhibitors, CPI-17, PHI-1, and KEPI, by various kinases. Protein kinases A (PKA) and G (PKG) phosphorylated CPI-17 at the inhibitory site (T38), but not PHI-1 (T57). Phosphorylated CPI-17 inhibited the activity of both the PP1 catalytic subunit (PP1c) and the myosin phosphatase holoenzyme (MPH) with IC50 values of 1-8nM. PKA predominantly phosphorylated a site distinct from the inhibitory T73 in KEPI, whereas PKG was ineffective. Integrin-linked kinase phosphorylated KEPI (T73) and this dramatically increased inhibition of PP1c (IC50=0.1nM) and MPH (IC50=8nM). These results suggest that the regulatory phosphorylation of CPI-17 and KEPI may involve distinct kinases and signaling pathways.",
keywords = "C-kinase-enhanced (potentiated) phosphatase inhibitors (CPI-17 and KEPI), Myosin phosphatase, Protein kinase A, Protein kinase G",
author = "F. Erdődi and Eniko Kiss and Walsh, {Michael P.} and Bjarki Stefansson and Deng, {Jing Ti} and Masumi Eto and Brautigan, {David L.} and Hartshorne, {David J.}",
year = "2003",
month = "6",
day = "27",
doi = "10.1016/S0006-291X(03)00976-8",
language = "English",
volume = "306",
pages = "382--387",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Phosphorylation of protein phosphatase type-1 inhibitory proteins by integrin-linked kinase and cyclic nucleotide-dependent protein kinases

AU - Erdődi, F.

AU - Kiss, Eniko

AU - Walsh, Michael P.

AU - Stefansson, Bjarki

AU - Deng, Jing Ti

AU - Eto, Masumi

AU - Brautigan, David L.

AU - Hartshorne, David J.

PY - 2003/6/27

Y1 - 2003/6/27

N2 - Protein phosphatases play key roles in cellular regulation and are subjected to control by protein inhibitors whose activity is in turn regulated by phosphorylation. Here we investigated the possible regulation of phosphorylation-dependent type-1 protein phosphatase (PP1) inhibitors, CPI-17, PHI-1, and KEPI, by various kinases. Protein kinases A (PKA) and G (PKG) phosphorylated CPI-17 at the inhibitory site (T38), but not PHI-1 (T57). Phosphorylated CPI-17 inhibited the activity of both the PP1 catalytic subunit (PP1c) and the myosin phosphatase holoenzyme (MPH) with IC50 values of 1-8nM. PKA predominantly phosphorylated a site distinct from the inhibitory T73 in KEPI, whereas PKG was ineffective. Integrin-linked kinase phosphorylated KEPI (T73) and this dramatically increased inhibition of PP1c (IC50=0.1nM) and MPH (IC50=8nM). These results suggest that the regulatory phosphorylation of CPI-17 and KEPI may involve distinct kinases and signaling pathways.

AB - Protein phosphatases play key roles in cellular regulation and are subjected to control by protein inhibitors whose activity is in turn regulated by phosphorylation. Here we investigated the possible regulation of phosphorylation-dependent type-1 protein phosphatase (PP1) inhibitors, CPI-17, PHI-1, and KEPI, by various kinases. Protein kinases A (PKA) and G (PKG) phosphorylated CPI-17 at the inhibitory site (T38), but not PHI-1 (T57). Phosphorylated CPI-17 inhibited the activity of both the PP1 catalytic subunit (PP1c) and the myosin phosphatase holoenzyme (MPH) with IC50 values of 1-8nM. PKA predominantly phosphorylated a site distinct from the inhibitory T73 in KEPI, whereas PKG was ineffective. Integrin-linked kinase phosphorylated KEPI (T73) and this dramatically increased inhibition of PP1c (IC50=0.1nM) and MPH (IC50=8nM). These results suggest that the regulatory phosphorylation of CPI-17 and KEPI may involve distinct kinases and signaling pathways.

KW - C-kinase-enhanced (potentiated) phosphatase inhibitors (CPI-17 and KEPI)

KW - Myosin phosphatase

KW - Protein kinase A

KW - Protein kinase G

UR - http://www.scopus.com/inward/record.url?scp=0037532608&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037532608&partnerID=8YFLogxK

U2 - 10.1016/S0006-291X(03)00976-8

DO - 10.1016/S0006-291X(03)00976-8

M3 - Article

VL - 306

SP - 382

EP - 387

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 2

ER -