Skip to main content

The regulation of smooth muscle contractility by zipper-interacting protein kinase

Buy Article:

$50.00 plus tax (Refund Policy)

Abstract:

Smooth muscle contractility is mainly regulated by phosphorylation of the 20 kDa myosin light chains (LC20), a process that is controlled by the opposing activities of myosin light chain kinase (MLCK) and myosin light chain phosphatase (MLCP). Recently, intensive research has revealed that various protein kinase networks including Rho-kinase, integrin-linked kinase, zipper-interacting protein kinase (ZIPK), and protein kinase C (PKC) are involved in the regulation of LC20 phosphorylation and have important roles in modulating smooth muscle contractile responses to Ca2+ (i.e., Ca2+ sensitization and Ca2+ desensitization). Here, we review the general background and structure of ZIPK and summarize our current understanding of its involvement in a number of cell processes including cell death (apoptosis), cell motility, and smooth muscle contraction. ZIPK has been found to induce the diphosphorylation of LC20 at Ser-19 and Thr-18 in a Ca2+-independent manner and to regulate MLCP activity directly through its phosphorylation of the myosin-targeting subunit of MLCP or indirectly through its phosphorylation of the PKC-potentiated inhibitory protein of MLCP. Future investigations of ZIPK function in smooth muscle will undoubtably focus on determining the mechanisms that regulate its cellular activity, including the identification of upstream signaling pathways, the characterization of autoinhibitory domains and regulatory phosphorylation sites, and the development of specific inhibitor compounds.

La contractilité du muscle lisse est régulée principalement par la phosphorylation des chaînes légères de la myosine de 20 kDa (CL20), un processus qui est régi par les activités antagonistes de la kinase (MLCK) et de la phosphatase (MLCP) de la chaîne légère de la myosine. Récemment, une recherche intensive a révélé que divers réseaux de protéines kinases, notamment la Rho-kinase, la kinase associée aux intégrines (ILK), la protéine kinase interagissant avec les motifs de type fermeture éclair (zipper) (ZIPK) et la protéine kinase C (PKC), sont impliqués dans la régulation de la phosphorylation des CL20 et ont des rôles importants dans la modulation des réponses contractiles du muscle lisse au Ca2+ (c.-à-d. sensibilisation et désensibilisation au Ca2+ ). Dans le présent article, nous faisons un rappel du contexte historique et de la structure de la ZIPK, et résumons notre compréhension de son rôle dans plusieurs processus cellulaires, y compris la mort cellulaire (apoptose), la motilité cellulaire et la contraction du muscle lisse. Il s’est révélé que la ZIPK provoque la déphosphorylation des CL20 au niveau de Ser-19 et Thr-18 d’une manière indépendante du Ca2+ et qu’elle régule l’activité de la MLCP directement par la phosphorylation de la sous-unité de la MLCP ciblant la myosine (MYPT-1) ou indirectement par la phosphorylation de la protéine inhibitrice de la MLCP potentialisée par la protéine kinase C. D’autres études de la fonction de la ZIPK dans le muscle lisse seront assurément axées sur la détermination des mécanismes qui régulent son activité cellulaire, y compris l’identification des voies de signalisation en aval, la caractérisation des domaines autoinhibiteurs et des sites régulateurs de la phosphorylation, et le développement de composés inhibiteurs spécifiques.

Document Type: Research Article

Publication date: January 1, 2007

More about this publication?
  • Published since 1929, this monthly journal reports current research in all aspects of physiology, nutrition, pharmacology, and toxicology, contributed by recognized experts and scientists. It publishes symposium reviews and award lectures and occasionally dedicates entire issues or portions of issues to subjects of special interest to its international readership.
  • Information for Authors
  • Submit a Paper
  • Subscribe to this Title
  • Terms & Conditions
  • Sample Issue
  • Reprints & Permissions
  • ingentaconnect is not responsible for the content or availability of external websites
nrc/cjpp/2007/00000085/00000001/art00009
dcterms_title,dcterms_description,pub_keyword
6
5
20
40
5

Access Key

Free Content
Free content
New Content
New content
Open Access Content
Open access content
Subscribed Content
Subscribed content
Free Trial Content
Free trial content
Cookie Policy
X
Cookie Policy
ingentaconnect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more