Tóth A, Kiss E, Gergely P, Walsh M P, Hartshorne D J, Erdödi F
Department of Medical Chemistry, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
FEBS Lett. 2000 Nov 3;484(2):113-7. doi: 10.1016/s0014-5793(00)02138-4.
The effect of phosphorylation in the N-terminal region of myosin phosphatase target subunit 1 (MYPT1) on the interactions with protein phosphatase 1 catalytic subunit (PP1c) and with phosphorylated 20 kDa myosin light chain (P-MLC20) was studied. Protein kinase C (PKC) phosphorylated threonine-34 (1 mol/mol), the residue preceding the consensus PP1c-binding motif ((35)KVKF(38)) in MYPT1(1-38), but this did not affect binding of the peptide to PP1c. PKC incorporated 2 mol P(i) into MYPT1(1-296) suggesting a second site of phosphorylation within the ankyrin repeats (residues 40-296). This phosphorylation diminished the stimulatory effect of MYPT1(1-296) on the P-MLC20 phosphatase activity of PP1c. Binding of PP1c or P-MLC20 to phosphorylated MYPT1(1-296) was also attenuated. It is concluded that phosphorylation of MYPT1 by PKC may therefore result in altered dephosphorylation of myosin.
研究了肌球蛋白磷酸酶靶向亚基1（MYPT1）N端区域的磷酸化对其与蛋白磷酸酶1催化亚基（PP1c）以及与磷酸化的20 kDa肌球蛋白轻链（P-MLC20）相互作用的影响。蛋白激酶C（PKC）使MYPT1（1-38）中苏氨酸-34（1摩尔/摩尔）磷酸化，该残基位于MYPT1中共有PP1c结合基序（(35)KVKF(38)）之前，但这并不影响该肽与PP1c的结合。PKC将2摩尔无机磷酸（Pi）掺入MYPT1（1-296），提示锚蛋白重复序列（残基40-296）内存在第二个磷酸化位点。这种磷酸化减弱了MYPT1（1-296）对PP1c的P-MLC20磷酸酶活性的刺激作用。PP1c或P-MLC20与磷酸化的MYPT1（1-296）的结合也减弱。因此得出结论，PKC介导的MYPT1磷酸化可能导致肌球蛋白去磷酸化改变。
