Singh S S, Chauhan A, Brockerhoff H, Chauhan V P
NYS Institute for Basic Research in Developmental Disabilities, Staten Island, N.Y. 10314, USA.
Life Sci. 1995;57(7):685-94. doi: 10.1016/0024-3205(95)00320-6.
The metabolism of phosphoinositides plays an important role in the signal transduction pathways. We report here that naturally occurring polyamines affect the activities of phosphatidylinositol (PI) 3-kinase and PI 4-phosphate (PIP) 5-kinase differently. While polyamines inhibited the PI 3-kinase activity, they stimulated the activity of PIP 5-kinase in the order of spermine > spermidine > putrescine. Spermine inhibited the PI 3-kinase activity in a concentration-dependent manner with an IC50 of 100 microM. On the other hand, spermine (5 mM) stimulated the activity of PIP 5-kinase 2-3 fold. Kinetic studies of spermine-mediated inhibition of PI 3-kinase revealed that it was noncompetitive with respect to ATP. The effect of Mg2+ and PIP2 concentration on kinase activity was sigmoidal, with spermine inhibiting PI 3-kinase activity at all PIP2 concentrations. While 1 mM calcium stimulated PI 3-kinase activity at submaximal concentrations of Mg2+ (1.25 mM), inhibition was observed at optimal concentration of Mg2+ (2 mM). We propose that spermine may modulate the cellular signal by virtue of its differential effects on phosphoinositide kinases.
磷酸肌醇的代谢在信号转导途径中起重要作用。我们在此报告，天然存在的多胺对磷脂酰肌醇（PI）3激酶和PI 4磷酸（PIP）5激酶的活性有不同影响。多胺抑制PI 3激酶活性，而它们以精胺>亚精胺>腐胺的顺序刺激PIP 5激酶的活性。精胺以浓度依赖的方式抑制PI 3激酶活性，IC50为100 microM。另一方面，精胺（5 mM）刺激PIP 5激酶的活性2至3倍。精胺介导的对PI 3激酶抑制的动力学研究表明，它对ATP是非竞争性的。Mg2+和PIP2浓度对激酶活性的影响呈S形，精胺在所有PIP2浓度下均抑制PI 3激酶活性。虽然1 mM钙在亚最大浓度的Mg2+（1.25 mM）下刺激PI 3激酶活性，但在最佳浓度的Mg2+（2 mM）下观察到抑制作用。我们提出，精胺可能凭借其对磷酸肌醇激酶的不同作用来调节细胞信号。
