Induction of MAPK phosphorylation by prosaposin and prosaptide in PC12 cells
Induction of MAPK phosphorylation by prosaposin and prosaptide in PC12 cells
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DOI：
10.1006/bbrc.1996.1869
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发表时间：
1996-12-24
影响因子：
3.1
通讯作者：
OBrien, JS
中科院分区：
文献类型：
--
作者：
Campana, WM;Hiraiwa, M;OBrien, JS
鞘脂激活蛋白原是一种66 kDa的糖蛋白，在体外和体内具有神经营养活性。鞘脂激活蛋白原内的神经营养序列（（8）CEFLVKEVTKLIDNNKTEKEL（29）L）位于鞘脂激活蛋白C结构域的氨基末端部分。这种22-mer肽，prosaptide，具有与saposin原相当的神经营养活性。我们目前的结合研究，使用I-125-saposin和I-125-prosaptide揭示了一个单一的类的特异性结合位点的Kd值分别为2.5 nM和18.3 nM。在PC 12细胞中，saposin和prosaptide均能迅速刺激蛋白酪氨酸磷酸化，使MAPK磷酸化增加20倍，尤其是p44 MAPK，其磷酸化在刺激5 min时达到峰值，然后迅速下降。用突变的22-mer前肽（（21）Asn至（21）Asp）处理PC 12细胞未诱导磷酸化。这些发现表明MAPK在鞘脂激活蛋白原的信号转导中的作用。(C)1996学术出版社
Prosaposin is a 66 kDa glycoprotein which has neurotrophic activity in vitro and in vivo. The neurotrophic sequence ((8)CEFLVKEVTKLIDNNKTEKEL(29)L) within prosaposin has been located to the amino terminal portion of the saposin C domain. This 22-mer peptide, prosaptide, has neurotrophic activity equivalent to prosaposin. We present binding studies using I-125-prosaposin and I-125-prosaptide which revealed a single class of specific binding sites with a Kd of 2.5 nM and 18.3 nM, respectively. Both prosaposin and prosaptide rapidly stimulated protein tyrosine phosphorylation in PC12 cells and increased phosphorylation of MAPK 20-fold especially of p44 MAPK which peaked at 5 minutes of stimulation and then rapidly declined. Treatment of PC12 cells with a mutant 22-mer prosaptide ((21)Asn to (21)Asp) did not induce phosphorylation. These findings suggest a role for MAPK in signal transduction by prosaposin. (C) 1996 Academic Press