Transduction of the N-Terminal Fragments of MYPT1 Enhances Myofilament Ca2+ Sensitivity in an Intact Coronary Artery

Katsuya Hirano, Dmitry N. Derkach, Mayumi Hirano, Junji Nishimura, Shosuke Takahashi, Hideo Kanaide

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11 Citations (Scopus)


Objective - The region of the 110 kDa regulatory subunit (MYPT1) of smooth muscle myosin phosphatase involved in the regulation of contraction was determined under physiological conditions. Methods and Results - Using HIV Tat protein-mediated protein transduction, the N-terminal fragments of MYPT1 were introduced to the intact porcine coronary arterial strips. Pre-incubation with 3 μmol/L TAT-MYPT11-374, a construct containing the Tat peptide and the residues 1 to 374 of MYPT1, for 15 minutes augmented (2.4-fold) the subsequent contraction induced by adding 1.25 mmol/L of extracellular Ca 2+ under 118 mmol/L K+ depolarization, with no augmentation of the [Ca2+]i elevation. The deletion of the Tat peptide, MYPT11-374, abolished the augmenting effect. TAT-MYPT11-296 demonstrated a weaker but significant augmentation (1.7-fold). However, TAT-MYPT11-171, TAT-MYPT139-374, TAT-MYPT139-296, and TAT-MYPT1297-374 had no augmenting activity. The myosin light chain phosphorylation level as a function of extracellular Ca2+ concentrations was shifted to the left in the strips pretreated with TAT-MYPT11-374 compared with the control. Conclusions - Region 1 to 296 was the minimal region involved in the enhancement of contraction, and region 297 to 374 played a supplemental role. These results suggested that the interaction mainly between catalytic subunit and MYPT1 play a critical role in the regulation of the endogenous myosin phosphatase in intact smooth muscle.

Original languageEnglish
Pages (from-to)464-469
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Issue number3
Publication statusPublished - Mar 2004

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine


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