p21-activated kinase increases the calcium sensitivity of rat triton-skinned cardiac muscle fiber bundles via a mechanism potentially involving novel phosphorylation of troponin I

Nina Buscemi, Darren Brian Foster, Irina Neverova, Jennifer E. Van Eyk

Research output: Contribution to journalArticle

Abstract

Phosphorylation of myofilament proteins by kinases such as cAMP-dependent protein kinase and protein kinase C has been shown to lead to altered thin-filament protein-protein interactions and modulation of cardiac function in vitro. In the present study, we report that a small GTPase-dependent kinase, p21-activated kinase (PAK), increases the calcium sensitivity of Triton-skinned cardiac muscle fiber bundles. Constitutively active PAK3 caused an average 1.25-fold (25.0±6.0%, n=6) increase in force at pCa 5.75, 1.44-fold (44.0±7.78%, n=6) at pCa 6.25, and 2.41-fold (141.2±23.7%, n=4) at pCa 6.5, representing a change in pCa50 value of approximately 0.25. Constitutively active PAK3 produced no change in force under conditions of relaxation (pCa 8.0) or maximal contraction (pCa 4.5). Furthermore, an inactive, kinase-dead form of PAK3 failed to produce any change in force development at any pCa value. The myofilament proteins phosphorylated by PAK3, at pCa 6.5, are desmin, troponin T, troponin I, and an unidentified 70-kDa protein. Importantly, cardiac troponin I was found to be phosphorylated at serine 149 of human cardiac troponin I, representing a novel phosphorylation site. These findings suggest a novel mechanism of modulating the calcium sensitivity of cardiac muscle contraction.

Original languageEnglish (US)
Pages (from-to)509-516
Number of pages8
JournalCirculation Research
Volume91
Issue number6
DOIs
StatePublished - Sep 20 2002
Externally publishedYes

Fingerprint

p21-Activated Kinases
Troponin I
Myocardium
Phosphorylation
Calcium
Myofibrils
Proteins
Phosphotransferases
Troponin T
Desmin
Monomeric GTP-Binding Proteins
Muscle Contraction
Cyclic AMP-Dependent Protein Kinases
Protein Kinases
Serine
Protein Kinase C

Keywords

  • Calcium
  • Cardiac
  • p21-activated kinase
  • Phosphorylation
  • Troponin I

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

p21-activated kinase increases the calcium sensitivity of rat triton-skinned cardiac muscle fiber bundles via a mechanism potentially involving novel phosphorylation of troponin I. / Buscemi, Nina; Foster, Darren Brian; Neverova, Irina; Van Eyk, Jennifer E.

In: Circulation Research, Vol. 91, No. 6, 20.09.2002, p. 509-516.

Research output: Contribution to journalArticle

@article{711ca3d0e6ed4f68b13b78a7ff7c8211,
title = "p21-activated kinase increases the calcium sensitivity of rat triton-skinned cardiac muscle fiber bundles via a mechanism potentially involving novel phosphorylation of troponin I",
abstract = "Phosphorylation of myofilament proteins by kinases such as cAMP-dependent protein kinase and protein kinase C has been shown to lead to altered thin-filament protein-protein interactions and modulation of cardiac function in vitro. In the present study, we report that a small GTPase-dependent kinase, p21-activated kinase (PAK), increases the calcium sensitivity of Triton-skinned cardiac muscle fiber bundles. Constitutively active PAK3 caused an average 1.25-fold (25.0±6.0{\%}, n=6) increase in force at pCa 5.75, 1.44-fold (44.0±7.78{\%}, n=6) at pCa 6.25, and 2.41-fold (141.2±23.7{\%}, n=4) at pCa 6.5, representing a change in pCa50 value of approximately 0.25. Constitutively active PAK3 produced no change in force under conditions of relaxation (pCa 8.0) or maximal contraction (pCa 4.5). Furthermore, an inactive, kinase-dead form of PAK3 failed to produce any change in force development at any pCa value. The myofilament proteins phosphorylated by PAK3, at pCa 6.5, are desmin, troponin T, troponin I, and an unidentified 70-kDa protein. Importantly, cardiac troponin I was found to be phosphorylated at serine 149 of human cardiac troponin I, representing a novel phosphorylation site. These findings suggest a novel mechanism of modulating the calcium sensitivity of cardiac muscle contraction.",
keywords = "Calcium, Cardiac, p21-activated kinase, Phosphorylation, Troponin I",
author = "Nina Buscemi and Foster, {Darren Brian} and Irina Neverova and {Van Eyk}, {Jennifer E.}",
year = "2002",
month = "9",
day = "20",
doi = "10.1161/01.RES.0000035246.27856.53",
language = "English (US)",
volume = "91",
pages = "509--516",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - p21-activated kinase increases the calcium sensitivity of rat triton-skinned cardiac muscle fiber bundles via a mechanism potentially involving novel phosphorylation of troponin I

AU - Buscemi, Nina

AU - Foster, Darren Brian

AU - Neverova, Irina

AU - Van Eyk, Jennifer E.

PY - 2002/9/20

Y1 - 2002/9/20

N2 - Phosphorylation of myofilament proteins by kinases such as cAMP-dependent protein kinase and protein kinase C has been shown to lead to altered thin-filament protein-protein interactions and modulation of cardiac function in vitro. In the present study, we report that a small GTPase-dependent kinase, p21-activated kinase (PAK), increases the calcium sensitivity of Triton-skinned cardiac muscle fiber bundles. Constitutively active PAK3 caused an average 1.25-fold (25.0±6.0%, n=6) increase in force at pCa 5.75, 1.44-fold (44.0±7.78%, n=6) at pCa 6.25, and 2.41-fold (141.2±23.7%, n=4) at pCa 6.5, representing a change in pCa50 value of approximately 0.25. Constitutively active PAK3 produced no change in force under conditions of relaxation (pCa 8.0) or maximal contraction (pCa 4.5). Furthermore, an inactive, kinase-dead form of PAK3 failed to produce any change in force development at any pCa value. The myofilament proteins phosphorylated by PAK3, at pCa 6.5, are desmin, troponin T, troponin I, and an unidentified 70-kDa protein. Importantly, cardiac troponin I was found to be phosphorylated at serine 149 of human cardiac troponin I, representing a novel phosphorylation site. These findings suggest a novel mechanism of modulating the calcium sensitivity of cardiac muscle contraction.

AB - Phosphorylation of myofilament proteins by kinases such as cAMP-dependent protein kinase and protein kinase C has been shown to lead to altered thin-filament protein-protein interactions and modulation of cardiac function in vitro. In the present study, we report that a small GTPase-dependent kinase, p21-activated kinase (PAK), increases the calcium sensitivity of Triton-skinned cardiac muscle fiber bundles. Constitutively active PAK3 caused an average 1.25-fold (25.0±6.0%, n=6) increase in force at pCa 5.75, 1.44-fold (44.0±7.78%, n=6) at pCa 6.25, and 2.41-fold (141.2±23.7%, n=4) at pCa 6.5, representing a change in pCa50 value of approximately 0.25. Constitutively active PAK3 produced no change in force under conditions of relaxation (pCa 8.0) or maximal contraction (pCa 4.5). Furthermore, an inactive, kinase-dead form of PAK3 failed to produce any change in force development at any pCa value. The myofilament proteins phosphorylated by PAK3, at pCa 6.5, are desmin, troponin T, troponin I, and an unidentified 70-kDa protein. Importantly, cardiac troponin I was found to be phosphorylated at serine 149 of human cardiac troponin I, representing a novel phosphorylation site. These findings suggest a novel mechanism of modulating the calcium sensitivity of cardiac muscle contraction.

KW - Calcium

KW - Cardiac

KW - p21-activated kinase

KW - Phosphorylation

KW - Troponin I

UR - http://www.scopus.com/inward/record.url?scp=0037144667&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037144667&partnerID=8YFLogxK

U2 - 10.1161/01.RES.0000035246.27856.53

DO - 10.1161/01.RES.0000035246.27856.53

M3 - Article

C2 - 12242269

AN - SCOPUS:0037144667

VL - 91

SP - 509

EP - 516

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 6

ER -