A glucagon fragment is responsible for the inhibition of the liver Ca2+ pump by glucagon
A glucagon fragment is responsible for the inhibition of the liver Ca2+ pump by glucagon
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胰高血糖素片段负责胰高血糖素抑制肝脏 Ca2 泵
作者：
A. Mallat;C. Pavoine;M. Dufour;S. Lotersztajn;D. Bataille;F. Pecker
胰高血糖素特异性抑制肝质膜中的Ca 2+泵，与腺苷酸环化酶激活无关1。然而，这种抑制作用仅在高浓度胰高血糖素（Ki = 0.7 µM）下观察到。此外，在存在杆菌肽（胰高血糖素降解抑制剂2）的情况下，Ca 2+泵对胰高血糖素不再敏感3。这些发现表明胰高血糖素片段可能是肝钙泵的真正效应物。碱性氨基酸对被认为是肽序列翻译后加工中的潜在切割位点4 -6。胰高血糖素分子包括二元双联体（Arg 17-Arg 18）。因此，我们研究了胰高血糖素（19-29）对肝钙泵的作用。该肽通过胰蛋白酶裂解从胰高血糖素中获得，并通过反相高效液相色谱法分离。我们发现，胰高血糖素（19-29）对腺苷酸环化酶的激活完全无效，但它能抑制肝质膜中Ca 2+激活和Mg 2+依赖的ATP酶活性（（Ca 2 +-Mg 2+）ATP酶）和Ca 2+转运，其效率比胰高血糖素高1,000倍。胰高血糖素（1 -21）完全无活性;胰高血糖素（18-29）和胰高血糖素（22-29）仅作为胰高血糖素（19-29）的部分激动剂起作用。这些结果表明，胰高血糖素（19-29），通过胰高血糖素的蛋白水解裂解获得，可能是参与抑制肝Ca 2+泵的活性肽。我们认为胰高血糖素可能是至少一种生物活性肽的前体。
Glucagon specifically inhibits the Ca2+ pump in liver plasma membranes independently of adenylate cyclase activation1. However, this inhibition is only observed at high concentrations of glucagon (Ki = 0.7 µM). Moreover, in the presence of bacitracin, an inhibitor of glucagon degradation2, the Ca2+ pump is no longer sensitive to glucagon3. These findings suggest that a fragment of glucagon might be the true effector of the liver Ca2+ pump. Pairs of basic amino acids are recognized as potential cleavage sites in post-translational processing of peptide hormones4–6. The glucagon molecule includes a dibasic doublet (Arg 17–Arg 18). Therefore, we have examined the action of glucagon( 19–29) on the liver Ca2+ pump. This peptide was obtained from glucagon by tryptic cleavage and separated by reverse-phase high-performance liquid chromatography. We found that glucagon( 19–29), which is totally ineffective in activating adenylate cyclase, inhibited both the Ca2+-activated and Mg2+-dependent ATPase activity ((Ca2+-Mg2+) ATPase) and Ca2+ transport in liver plasma membranes with an efficiency 1,000-fold higher than that of glucagon. Glucagon(l–21) was completely inactive; glucagon( 18–29) and glucagon(22–29) acted only as partial agonists of glucagon( 19–29). These results indicate that glucagon( 19–29), obtained by proteolytic cleavage of glucagon, is likely to be the active peptide involved in the inhibition of the liver Ca2+ pump. We suggest that glucagon may be a precursor of at least one biologically active peptide.
兔肝质膜对生长激素的裂解增强了结合。
DOI：
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发表时间：
1984
期刊：
The Journal of biological chemistry
影响因子：
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作者：
Schepper,JM;Hughes,EF;Postel-Vinay,MC;Hughes,JP
通讯作者：
Hughes,JP
DOI：
10.1016/s0021-9258(17)39531-5
发表时间：
1985-07
期刊：
The Journal of biological chemistry
影响因子：
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作者：
R. A. Snyder;K. Watt;B. Wintroub
通讯作者：
R. A. Snyder;K. Watt;B. Wintroub
胰高血糖素基因序列。
DOI：
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发表时间：
1984
期刊：
The Journal of biological chemistry
影响因子：
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作者：
Heinrich,G;Gros,P;Habener,JF
通讯作者：
Habener,JF