Document Detail


Unphosphorylated MARCKS is involved in neurite initiation induced by insulin-like growth factor-I in SH-SY5Y cells.
MedLine Citation:
PMID:  16941482     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Myristoylated alanine-rich C kinase substrate (MARCKS) has been suggested to be involved in various aspects of neuronal cell differentiation, including neurite outgrowth. However, the precise mechanisms by which MARCKS phosphorylation is regulated, and how MARCKS contributes to neurite outgrowth, are poorly understood. Here, we found that treatment of SH-SY5Y cells with insulin-like growth factor-I (IGF-I) induced a rapid and transient decrease in the level of phosphorylated MARCKS (P-MARCKS) to below the basal level. The decrease in P-MARCKS induced by IGF-I was blocked by pretreatment of cells with phosphoinositide 3-kinase (PI3K) inhibitors, LY294002 and wortmannin. A decrease in P-MARCKS was also observed in cells treated with a Rho-dependent kinase (ROCK) inhibitor, Y27632. Furthermore, IGF-I induced transient inactivation of RhoA, an upstream effector of ROCK. We showed that MARCKS was translocated to the membrane and colocalized with F-actin at the lamellipodia and the tips of neurites in the cells stimulated with IGF-I. Finally, overexpression of wild-type MARCKS or an unphosphorylatable mutant of MARCKS enhanced the number of neurite-bearing cells relative to vector-transfected cells. Taken together, these findings suggest that unphosphorylated MARCKS is involved in neurite initiation, and highlight the important role played by MARCKS in organization of the actin cytoskeleton.
Authors:
Mitsuya Shiraishi; Atsuhiro Tanabe; Naoaki Saito; Yasuharu Sasaki
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  209     ISSN:  0021-9541     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-10-02     Completed Date:  2007-02-07     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1029-38     Citation Subset:  IM    
Copyright Information:
(c) 2006 Wiley-Liss, Inc.
Affiliation:
Laboratory of Pharmacology, School of Pharmaceutical Science, Kitasato University, Shirokane 5-9-1, Minato-ku, Tokyo 108-8641, Japan. shiraishim@pharm.kitasato-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / antagonists & inhibitors,  metabolism
Actins / metabolism
Androstadienes / metabolism
Cell Line, Tumor
Cell Membrane / metabolism
Chromones / metabolism
Enzyme Inhibitors / metabolism
Humans
Insulin-Like Growth Factor I / metabolism,  pharmacology*
Intracellular Signaling Peptides and Proteins / genetics,  metabolism*
Membrane Proteins / genetics,  metabolism*
Morpholines / metabolism
Neurites / drug effects*,  metabolism*,  ultrastructure
Neuroblastoma / metabolism*
Phosphoprotein Phosphatases / antagonists & inhibitors,  metabolism
Phosphorylation
Protein-Serine-Threonine Kinases / metabolism
Signal Transduction / physiology
rho-Associated Kinases
rhoA GTP-Binding Protein / metabolism
Chemical
Reg. No./Substance:
0/Actins; 0/Androstadienes; 0/Chromones; 0/Enzyme Inhibitors; 0/Intracellular Signaling Peptides and Proteins; 0/Membrane Proteins; 0/Morpholines; 125267-21-2/myristoylated alanine-rich C kinase substrate; 154447-36-6/2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; 19545-26-7/wortmannin; 67763-96-6/Insulin-Like Growth Factor I; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/rho-Associated Kinases; EC 3.1.3.16/Phosphoprotein Phosphatases; EC 3.6.5.2/rhoA GTP-Binding Protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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