Hübner S, Couvillon A D, Käs J A, Bankaitis V A, Vegners R, Carpenter C L, Janmey P A
Experimental Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
Eur J Biochem. 1998 Dec 1;258(2):846-53. doi: 10.1046/j.1432-1327.1998.2580846.x.
The phosphorylation of phosphatidylinositol (PtdIns) on the 3' position of the inositol ring by phosphoinositide 3-kinase (PI 3-kinase) is shown to depend strongly on the curvature of liposomes containing a mixture of phosphatidylcholine (PtdCho) and PtdIns. Vesicles with an average diameter of 50 nm are phosphorylated 100 times faster than chemically identical vesicles with an average diameter greater than 300 nm. The low reactivity of large vesicles is not due to the difference in vesicle number for large and small vesicles at constant total lipid, nor to occlusion of lipid surfaces in multilammelar structures, and can be reversed by addition of low (< 1:100) molar ratios of either the PtdIns transfer protein sec14p or a ten-residue peptide derived from the inositol-phospholipid-binding site of gelsolin. Similar measurements using PI 4-kinase showed a weak dependence on vesicle size. The strong dependence of PI 3-kinase function on membrane curvature suggests possible localization of PI 3-kinase activity at sites where clustering of receptors, for example, may locally deform the membrane, and suggests that once PI 3-kinase is localized and activated at surface sites, the reaction may become self-accelerating.
磷酸肌醇3激酶（PI 3激酶）使肌醇环3'位的磷脂酰肌醇（PtdIns）磷酸化，这一过程被证明强烈依赖于含有磷脂酰胆碱（PtdCho）和PtdIns混合物的脂质体的曲率。平均直径为50 nm的囊泡的磷酸化速度比平均直径大于300 nm的化学组成相同的囊泡快100倍。大囊泡的低反应性不是由于在总脂质恒定的情况下大、小囊泡的囊泡数量差异，也不是由于多层结构中脂质表面的封闭，并且可以通过添加低（<1:100）摩尔比的PtdIns转移蛋白sec14p或源自凝溶胶蛋白肌醇磷脂结合位点的十肽来逆转。使用PI 4激酶进行的类似测量显示对囊泡大小的依赖性较弱。PI 3激酶功能对膜曲率的强烈依赖性表明PI 3激酶活性可能定位于例如受体聚集可能使膜局部变形的位点，并且表明一旦PI 3激酶在表面位点定位并被激活，反应可能会自我加速。
