文献类型：期刊文献

英文题名：Palmitoylation modification of G alpha(o) depresses its susceptibility to GAP-43 activation

作者：Yang, Hui[1];Wan, Lixin[1,2];Song, Fuchun[3];Wang, Mengxi[4];Huang, Youguo[1]

第一作者：Yang, Hui

通讯作者：Huang, YG[1]

机构：[1]Chinese Acad Sci, Nat Lab Biomacromol, Inst Biophys, Beijing 100101, Peoples R China;[2]Chinese Acad Sci, Grad Sch, Beijing 10049, Peoples R China;[3]Beijing Union Univ, Teachers Coll, Beijing 100011, Peoples R China;[4]Peking Univ, Dept Biol, Beijing 100871, Peoples R China

第一机构：Chinese Acad Sci, Nat Lab Biomacromol, Inst Biophys, Beijing 100101, Peoples R China

通讯机构：[1]corresponding author), Chinese Acad Sci, Nat Lab Biomacromol, Inst Biophys, 15 Datun Rd, Beijing 100101, Peoples R China.

年份：2009

卷号：41

期号：7

起止页码：1495-1501

外文期刊名：INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000265768000007)】；

基金：This research was supported by the National Basic Research Program of China (Grants 2004CB720000 and 2006CB911001) and the Natural Science Foundation of China (30370350). We thank Dr. Duan Xiaoli at the Fourth Military Medical College for her generous gift of pGEX-4T-1-GAP-43 expression plasmid. We are grateful to Drs. Geir Skogerbo and Dennis Wolff and Joseph Kirui for their editorial assistance during the preparation of this manuscript in English.

语种：英文

外文关键词：GAP-43; G alpha(0); Palmitoylation; GTP gamma S binding activity; Oligomerization

摘要：Interaction between GAP-43 (growth associated protein-43) and G alpha(o) (alpha subunit of Go protein) influences the signal transduction pathways leading to differentiation of neural cells. GAP-43 is known to increase guanine nucleotide exchange by Gao, which is a major component of neuronal growth cone membranes. However, it is not clear whether GAP-43 stimulation is related to the Got, palmitoylation or the conversion of Goto from oligmers to monomers, which was shown to be a necessary regulatory factor in GDP/GTP exchange of G alpha(o). Here we expressed and purified GAP-43, GST-GAP-43 and Gao proteins, detected their stimulatory effect on [S-35]-GTP gamma S binding of G alpha(o). It was found that the EC50 of both GAP-43 and GST-GAP-43 activation were tenfold lower in case of depalmitoylated Ga. than palmitoylated Gao. Non-denaturing gel electrophoresis and p-PDM cross-linking analysis revealed that addition of GST-GAP-43 induced disassociation of depalmitoylated G alpha(o), from oligomers to monomers, but did not influence the oligomeric state of palmitoylated Gao, which suggests that palmitoylation is a key regulatory factor in GAP-43 stimulation on Ga,. These results indicated the interaction of GAP-43 and Goto could accelerate conversion of depalmitoylated Goto but not palmitoylated Get. from oligomers to monomers, so as to increase the GTP gamma S binding activity of G alpha(o). Results here provide new evidence about how signaling protein palmitoylation is involved in the G-protein-coupled signal transduction cascade, and give a useful clue on the participation of GAP-43 in G-protein cycle by its preferential activation of depalmitoylated G alpha(o). (c) 2008 Elsevier Ltd. All rights reserved.