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Cardiac myosin is a substrate for zipper-interacting protein kinase (ZIPK)

Audrey N Chang1, Guohua Chen, Robert D Gerard

  • 1Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.

The Journal of Biological Chemistry
|December 30, 2009
PubMed

Insights

Zipper-interacting protein kinase (ZIPK) phosphorylates cardiac myosin regulatory light chain (RLC) in heart cells. This finding suggests ZIPK may regulate cardiac contractility.

Area of Science:

  • Molecular Biology
  • Cardiovascular Research
  • Cell Signaling

Background:

  • Zipper-interacting protein kinase (ZIPK) is a death-associated protein kinase involved in apoptosis and membrane blebbing via myosin regulatory light chain (RLC) phosphorylation in nonmuscle cells.
  • ZIPK is highly expressed in cardiac tissue, including neonatal rat ventricular myocytes, suggesting a potential role in heart function.

Purpose of the Study:

  • To investigate whether ZIPK phosphorylates cardiac RLC and to characterize this interaction.
  • To determine the functional significance of ZIPK in cardiac myocytes regarding RLC phosphorylation and contractility.

Main Methods:

  • Purified ZIPK was used in an unbiased substrate search on heart homogenates to identify protein targets.
  • Biochemical analyses, including kinetic studies (Vmax), were performed to characterize ZIPK's phosphorylation of cardiac RLC.
  • Small interfering RNA (siRNA) was used to knock down ZIPK expression in cardiac myocytes to assess the impact on RLC phosphorylation.

Main Results:

  • Cardiac RLC was identified as a prominent 20-kDa substrate of ZIPK in heart homogenates.
  • ZIPK phosphorylated cardiac RLC at Ser-15 with a Vmax value twice as high as that for smooth/nonmuscle RLC, indicating cardiac RLC is a favorable substrate.
  • ZIPK knockdown in cardiac myocytes significantly reduced the extent of RLC Ser-15 phosphorylation.

Conclusions:

  • ZIPK acts as a cardiac RLC kinase, phosphorylating it at Ser-15.
  • ZIPK's role as a cardiac RLC kinase suggests it may influence cardiac contractility.
  • Further research is warranted to elucidate the precise mechanisms by which ZIPK affects cardiac function.

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