S3.5 Apoptosis of Burkitt's lymphoma cells via Gb3/CD77 a neutral glycolipid antigen
S3.5 Apoptosis of Burkitt's lymphoma cells via Gb3/CD77 a neutral glycolipid antigen
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S3.5 伯基特淋巴瘤细胞通过 Gb3/CD77（中性糖脂抗原）凋亡
DOI：
10.1007/bf01209876
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发表时间：
1993
影响因子：
3
通讯作者：
J. Wiels
中科院分区：
文献类型：
--
作者：
M. Mangeney;C. Lingwood;S. Taga;B. Caillou;T. Tursz;J. Wiels
神经节苷脂抑制钙调蛋白（CaM）刺激酶的活性。在没有钙调素的情况下，神经节苷脂在低浓度下刺激钙调素依赖性酶的活性，并在较高浓度下抑制活性。钙调素依赖性酶通过其钙调素结合位点（CBS）与钙调素样结合位点（CLBS）的结合来自我抑制活性，钙调素通过与CBS结合来释放它们的抑制。我们最近发现神经节苷脂与CaM结合，并提出了一个假设，即神经节苷脂具有CaM结合性质，通过与CaM和酶的CLBS结合来调节CaM依赖性酶（1-3）。在本研究中，我们研究了神经节苷脂和钙调素依赖酶的合成多肽之间的相互作用，以证实这一假设。由质膜Ca ~（2+），Mg ~（2+）-ATP酶CLBS的17个氨基酸残基组成的肽消除了神经节苷脂介导的对钙调素非依赖性刺激的cAMP磷酸二酯酶活性的抑制，表明该肽与神经节苷脂GD 1 B，GT 1b和GD 1a直接相互作用。另一方面，磷酸二酯酶、Ca 2+、MgE+-ATP酶和钙调神经磷酸酶的CBS合成肽也显示出相同的作用，表明CBS与神经节苷脂之间也存在相互作用。因此，我们在这里修改了模型的神经节苷脂介导的直接调制钙调素依赖性酶如下：没有钙调素，神经节苷脂刺激酶的活性相同的方式钙调素，结合CBS;并在较高的浓度，抑制活性相同的方式作为CBS的酶，结合CLBS。(1)Higashi，H. Yamagata，T.等人（1992）J.Biol.Chem.267，9839-9843。
Gangliosides inhibit the activity of calmodulin (CaM)-stimulated enzymes. Without CaM, gangliosides stimulate CaM-dependent enzyme activity at low concentrations and inhibit the activity at higher concentrations. CaM-dependent enzymes self-suppress the activity through binding of their CaM-binding site (CBS) to CaM-like binding site (CLBS), and CaM releases them from the suppression by binding to the CBS. We recently found that gangliosides bound to CaM and proposed a hypothesis that gangliosides, as they have CaM-binding nature, modulate CaM-dependent enzymes through binding to CaM and CLBSs of the enzymes (1-3). In the present study, we have examined interaction between gangliosides and synthetic polypeptides of CaM-dependent enzymes to confirm the hypothesis. A peptide consisting of 17 amino acid residues of a CLBS of plasma membrane Ca2+, Mg2+-ATPase has eliminated ganglioside-mediated inhibition of CaM-independently stimulated cAMP phosphodiesterase activity, indicating direct interaction of the peptide with ganglioside GD1 b, GTlb, and GDla. Unexpectedly, on the other hand, synthetic peptides of CBSs of phosphodiesterase, Ca 2+, MgE+-ATPase, and calcineurin have also shown the same effects, indicating that the interaction between CBS and gangliosides is also present. Thus we here have revised the model of ganglioside-mediated direct modulation of CaM-dependent enzymes as follows: Without CaM, gangliosides stimulate the enzyme activity by the same manner as CaM, binding to CBS; and at higher concentrations, inhibit the activity by the same manner as the CBS of the enzyme, binding to CLBS.(1) Higashi, H. and Yamagata, T.(1992) J. Biol. Chem. 267, 9839-9843.