Vascular smooth muscle contractile elements cellular regulation

James T. Stull, Patricia Gallagher, B. Herring, Kristine E. Kamm

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

For many years the simple view was held that contractile force in smooth muscle was proportional to cytosolic Ca2+ concentrations ([Ca2+],). With the discovery that phosphorylation of myosin light chain by Ca2VcaImodulin-dependent myosin light chain kinase initiated contraction, regulation of the contractile elements developed more complex properties. Molecular and biochemical investigations have identified important domains of myosin light chain kinase: light chain binding sites, catalytic core, pseudosubstrate prototope, and calmodulin-binding domain. New protein phosphatase inhibitors such as okadaic acid and calyculin A should help In the identification of the physiologically important phosphatase and potential modes of regulation. The proposal of an attached, dephosphorylated myosin cross bridge (latch bridge) that can maintain force has evoked considerable controversy about the detailed functions of the myosin phosphorylation system. The latch bridge has been defined by a model based on physiological properties but has not been identified biochemically. Thin-filament proteins have been proposed as secondary sites of regulation of contractile elements, but additional studies are needed to establish physiological roles. Changes in the Ca2+ sensitivity of smooth muscle contractile elements with different modes of cellular stimulation may be related to inactivation of myosin light chain kinase or activation of protein phosphatase activities. Thus, contractile elements in smooth muscle cells are not dependent solely on [Ca2+] but use additional regulatory mechanisms. The immediate challenge is to define their relative importance and to describe molecular-biochemical properties that provide insights into proposed physiological functions.

Original languageEnglish (US)
Pages (from-to)723-732
Number of pages10
JournalHypertension
Volume17
Issue number6
StatePublished - 1991
Externally publishedYes

Fingerprint

Myosin-Light-Chain Kinase
Vascular Smooth Muscle
Phosphoprotein Phosphatases
Myosins
Smooth Muscle
Phosphorylation
Okadaic Acid
Myosin Light Chains
Calmodulin
Phosphoric Monoester Hydrolases
Smooth Muscle Myocytes
Catalytic Domain
Binding Sites
Light
Proteins

Keywords

  • Calcium
  • Calmodulin
  • Contractile proteins
  • Myosin
  • Myosin light-chain kinase
  • Phosphorylation
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Stull, J. T., Gallagher, P., Herring, B., & Kamm, K. E. (1991). Vascular smooth muscle contractile elements cellular regulation. Hypertension, 17(6), 723-732.

Vascular smooth muscle contractile elements cellular regulation. / Stull, James T.; Gallagher, Patricia; Herring, B.; Kamm, Kristine E.

In: Hypertension, Vol. 17, No. 6, 1991, p. 723-732.

Research output: Contribution to journalArticle

Stull, JT, Gallagher, P, Herring, B & Kamm, KE 1991, 'Vascular smooth muscle contractile elements cellular regulation', Hypertension, vol. 17, no. 6, pp. 723-732.
Stull JT, Gallagher P, Herring B, Kamm KE. Vascular smooth muscle contractile elements cellular regulation. Hypertension. 1991;17(6):723-732.
Stull, James T. ; Gallagher, Patricia ; Herring, B. ; Kamm, Kristine E. / Vascular smooth muscle contractile elements cellular regulation. In: Hypertension. 1991 ; Vol. 17, No. 6. pp. 723-732.
@article{e84e6922f2574bd388accb40e18a352e,
title = "Vascular smooth muscle contractile elements cellular regulation",
abstract = "For many years the simple view was held that contractile force in smooth muscle was proportional to cytosolic Ca2+ concentrations ([Ca2+],). With the discovery that phosphorylation of myosin light chain by Ca2VcaImodulin-dependent myosin light chain kinase initiated contraction, regulation of the contractile elements developed more complex properties. Molecular and biochemical investigations have identified important domains of myosin light chain kinase: light chain binding sites, catalytic core, pseudosubstrate prototope, and calmodulin-binding domain. New protein phosphatase inhibitors such as okadaic acid and calyculin A should help In the identification of the physiologically important phosphatase and potential modes of regulation. The proposal of an attached, dephosphorylated myosin cross bridge (latch bridge) that can maintain force has evoked considerable controversy about the detailed functions of the myosin phosphorylation system. The latch bridge has been defined by a model based on physiological properties but has not been identified biochemically. Thin-filament proteins have been proposed as secondary sites of regulation of contractile elements, but additional studies are needed to establish physiological roles. Changes in the Ca2+ sensitivity of smooth muscle contractile elements with different modes of cellular stimulation may be related to inactivation of myosin light chain kinase or activation of protein phosphatase activities. Thus, contractile elements in smooth muscle cells are not dependent solely on [Ca2+] but use additional regulatory mechanisms. The immediate challenge is to define their relative importance and to describe molecular-biochemical properties that provide insights into proposed physiological functions.",
keywords = "Calcium, Calmodulin, Contractile proteins, Myosin, Myosin light-chain kinase, Phosphorylation, Vascular smooth muscle",
author = "Stull, {James T.} and Patricia Gallagher and B. Herring and Kamm, {Kristine E.}",
year = "1991",
language = "English (US)",
volume = "17",
pages = "723--732",
journal = "Hypertension",
issn = "0194-911X",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Vascular smooth muscle contractile elements cellular regulation

AU - Stull, James T.

AU - Gallagher, Patricia

AU - Herring, B.

AU - Kamm, Kristine E.

PY - 1991

Y1 - 1991

N2 - For many years the simple view was held that contractile force in smooth muscle was proportional to cytosolic Ca2+ concentrations ([Ca2+],). With the discovery that phosphorylation of myosin light chain by Ca2VcaImodulin-dependent myosin light chain kinase initiated contraction, regulation of the contractile elements developed more complex properties. Molecular and biochemical investigations have identified important domains of myosin light chain kinase: light chain binding sites, catalytic core, pseudosubstrate prototope, and calmodulin-binding domain. New protein phosphatase inhibitors such as okadaic acid and calyculin A should help In the identification of the physiologically important phosphatase and potential modes of regulation. The proposal of an attached, dephosphorylated myosin cross bridge (latch bridge) that can maintain force has evoked considerable controversy about the detailed functions of the myosin phosphorylation system. The latch bridge has been defined by a model based on physiological properties but has not been identified biochemically. Thin-filament proteins have been proposed as secondary sites of regulation of contractile elements, but additional studies are needed to establish physiological roles. Changes in the Ca2+ sensitivity of smooth muscle contractile elements with different modes of cellular stimulation may be related to inactivation of myosin light chain kinase or activation of protein phosphatase activities. Thus, contractile elements in smooth muscle cells are not dependent solely on [Ca2+] but use additional regulatory mechanisms. The immediate challenge is to define their relative importance and to describe molecular-biochemical properties that provide insights into proposed physiological functions.

AB - For many years the simple view was held that contractile force in smooth muscle was proportional to cytosolic Ca2+ concentrations ([Ca2+],). With the discovery that phosphorylation of myosin light chain by Ca2VcaImodulin-dependent myosin light chain kinase initiated contraction, regulation of the contractile elements developed more complex properties. Molecular and biochemical investigations have identified important domains of myosin light chain kinase: light chain binding sites, catalytic core, pseudosubstrate prototope, and calmodulin-binding domain. New protein phosphatase inhibitors such as okadaic acid and calyculin A should help In the identification of the physiologically important phosphatase and potential modes of regulation. The proposal of an attached, dephosphorylated myosin cross bridge (latch bridge) that can maintain force has evoked considerable controversy about the detailed functions of the myosin phosphorylation system. The latch bridge has been defined by a model based on physiological properties but has not been identified biochemically. Thin-filament proteins have been proposed as secondary sites of regulation of contractile elements, but additional studies are needed to establish physiological roles. Changes in the Ca2+ sensitivity of smooth muscle contractile elements with different modes of cellular stimulation may be related to inactivation of myosin light chain kinase or activation of protein phosphatase activities. Thus, contractile elements in smooth muscle cells are not dependent solely on [Ca2+] but use additional regulatory mechanisms. The immediate challenge is to define their relative importance and to describe molecular-biochemical properties that provide insights into proposed physiological functions.

KW - Calcium

KW - Calmodulin

KW - Contractile proteins

KW - Myosin

KW - Myosin light-chain kinase

KW - Phosphorylation

KW - Vascular smooth muscle

UR - http://www.scopus.com/inward/record.url?scp=0026006558&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026006558&partnerID=8YFLogxK

M3 - Article

VL - 17

SP - 723

EP - 732

JO - Hypertension

JF - Hypertension

SN - 0194-911X

IS - 6

ER -