Abstract
Zipper-interacting protein kinase (ZIPK) is a member of the death-associated protein kinase family associated with apoptosis in nonmuscle cells where it phosphorylates myosin regulatory light chain (RLC) to promote membrane blebbing. ZIPK mRNA and protein are abundant in heart tissue and isolated ventricular neonatal rat cardiac myocytes. An unbiased substrate search performed with purified ZIPK on heart homogenates led to the discovery of a prominent 20-kDa protein substrate identified as RLC of ventricular myosin. Biochemical analyses showed ZIPK phosphorylated cardiac RLC at Ser-15 with a V(max) value 2-fold greater than the value for smooth/nonmuscle RLC; cardiac RLC is a favorable biochemical substrate. Knockdown of ZIPK in cardiac myocytes by small interfering RNA significantly decreased the extent of RLC Ser-15 phosphorylation. Thus, ZIPK may act as a cardiac RLC kinase and thereby affect contractility.
Highlights
Myosin is the molecular motor in the thick filament of the sarcomere that binds to actin thin filaments to initiate myocyte shortening and force development when Ca2ϩ binds to troponin in the thin filament [1]
Previous investigations have focused on its respective roles in apoptosis in nonmuscle cells and contraction in smooth muscle, where studies on the latter were stimulated by identification of smooth muscle regulatory light chain (RLC) and the regulatory subunit of smooth muscle myosin light chain phosphatase (MYPT1) as substrates for Zipper-interacting protein kinase (ZIPK) [21, 23, 24]
ZIPK mRNA and Protein Are Expressed in the Heart—QPCR results showed ZIPK mRNA was abundant in mouse striated muscles relative to the amount in urinary bladder smooth muscle (Fig. 1A)
Summary
Myosin is the molecular motor in the thick filament of the sarcomere that binds to actin thin filaments to initiate myocyte shortening and force development when Ca2ϩ binds to troponin in the thin filament [1]. We found that cardiac RLC is phosphorylated by ZIPK at Ser-15 in vitro and in vivo, implicating a role for this protein kinase in modulating cardiac contractility.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
