Jahn H, Kiefer F, Behl C, Wiedemann K
Clinic of Psychiatry and Psychotherapy, University of Hamburg, Germany.
Neurochem Res. 2001 May;26(5):473-8. doi: 10.1023/a:1010900626316.
The discovery of free and membrane-bound ectokinases raises the question whether phosphorylation is another mechanism to modulate the action of distinct neuropeptides. Atrial-natriuretic-peptide (ANP) which is widespread found in the central nervous system (CNS) and involved in the modulation of stress reactions and emotional states like anxiety contains a recognition-motif for cAMP-dependent protein kinase A. We investigated the effect of phosphorylation of ANP and C-type natriuretic peptide (CNP), a related peptide without phosphorylation site, on their ability to activate their receptors in mouse pituitary AtT20 cells by measuring the formation of cyclic guanosinmonophosphate (cGMP). Phosphorylation with protein kinase A inactivated ANP. Coincubation experiments adding adenosintriphosphate (ATP), ATP-analogues or inhibitors of protein kinases to the medium pointed to the presence of an intrinsic protein kinase A like ectokinase-activity on AtT20 cells. The activity of CNP was unaffected in these experiments. Phosphorylation by ectokinases may be a physiological mechanism to regulate the biological activity of ANP in different tissues, such as pituitary and CNS.
游离和膜结合型胞外激酶的发现引发了一个问题，即磷酸化是否是调节不同神经肽作用的另一种机制。心房利钠肽（ANP）广泛存在于中枢神经系统（CNS）中，参与应激反应和焦虑等情绪状态的调节，它含有一个依赖cAMP的蛋白激酶A的识别基序。我们通过测量环磷酸鸟苷（cGMP）的形成，研究了ANP和C型利钠肽（CNP，一种无磷酸化位点的相关肽）磷酸化对其在小鼠垂体AtT20细胞中激活受体能力的影响。蛋白激酶A介导的磷酸化使ANP失活。向培养基中添加三磷酸腺苷（ATP）、ATP类似物或蛋白激酶抑制剂的共孵育实验表明，AtT20细胞上存在一种类似内在蛋白激酶A的胞外激酶活性。在这些实验中，CNP的活性未受影响。胞外激酶介导的磷酸化可能是调节ANP在不同组织（如垂体和中枢神经系统）中生物学活性的一种生理机制。
