Functional interaction of calcium-/calmodulin-dependent protein kinase II and cytosolic phospholipase A2
Functional interaction of calcium-/calmodulin-dependent protein kinase II and cytosolic phospholipase A2
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DOI：
10.1074/jbc.m103136200
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发表时间：
2001-10-26
影响因子：
4.8
通讯作者：
Malik, KU
中科院分区：
文献类型：
--
作者：
Muthalif, MM;Hefner, Y;Malik, KU
钙/钙调素依赖性蛋白激酶II （CaM激酶II）是Ca2+信号的解码器，细胞质磷脂酶a (2) （cPLA(2)）是一种参与花生四烯酸释放的酶，参与许多生理和病理生理过程。在去甲肾上腺素刺激的血管平滑肌细胞中，CaM激酶Il的激活导致cPLA(2)的激活和花生四烯酸的释放。表面等离子体共振、质谱和动力学研究表明，CaM激酶II与cPLA(2)结合，导致Ser-515上的cPLA(2)磷酸化，并增加其酶活性。从去甲肾上腺素刺激的平滑肌细胞中对cPLA(2)进行的磷酸肽定位研究表明，在体内，cPLA(2)在Ser-515上发生磷酸化，而在Ser-505或Ser-727上没有磷酸化。这种新的花生四烯酸酯释放信号通路通过使用最近描述的高选择性酶抑制剂被证明是依赖于cPLA(2)的。
Calcium-/calmodulin-dependent protein kinase II (CaM kinase II), a decoder of Ca2+ signals, and cytosolic phospholipase A(2) (cPLA(2)), an enzyme involved in arachidonate release, are involved in many physiological and pathophysiological processes. Activation of CaM kinase Il in norepinephrine-stimulated vascular smooth muscle cells leads to activation of cPLA(2) and arachidonic acid release. Surface plasmon resonance, mass spectrometry, and kinetic studies show that CaM kinase II binds to cPLA(2) resulting in cPLA(2) phosphorylation on Ser-515 and an increase in its enzymatic activity. Phosphopeptide mapping studies with cPLA(2) from norepinephrine-stimulated smooth muscle cells indicates that phosphorylation of cPLA(2) on Ser-515, but not on Ser-505 or Ser-727, occurs in vivo. This novel signaling pathway for arachidonate release is shown to be cPLA(2)-dependent by use of a recently described and highly selective inhibitor of this enzyme.