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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Suh, Han Na Han, Ho Jae |
| Description | Author Affiliation: Suh HN ( Dept. of Veterinary Physiology, Chonnam National Univ., Gwangju, Korea.) |
| Abstract | Laminin is the first extracellular matrix (ECM) component to be expressed in the developing mammalian embryo. However, the roles of laminin or the related signal pathways are not well known in mouse embryonic stem cells (mESCs). Presently, we examined the effect of laminin on mESC migration. Laminin (10 microg/ml) decreased cell aggregation, whereas migration was increased. Laminin bound alpha6beta1 integrin and laminin receptor 1 (LR1), decreasing their mRNA levels. Laminin increased focal adhesion kinase (FAK) and paxillin phosphorylation, cAMP intracellular concentration, and the protein levels of exchange factor directly activated by cAMP (Epac1) and Rap1. These increases were completely blocked by alpha6beta1 integrin and LR1 neutralizing antibody, indicating that laminin-bound LR1 assists laminin-induced alpha6beta1 integrin activity and initiates signal. As a downstream signal molecule, laminin activated small G protein such as Rac1/cdc42 and its effector protein p21-activated kinase (PAK). Subsequently, laminin stimulated E-cadherin complex disruption. Inhibition of each pathway such as those for alpha6beta1 integrin and LR1, FAK, Rap1, and PAK1 blocked laminin-induced migration. We conclude that laminin binds both alpha6beta1 integrin and LR1 and induces signaling FAK/paxillin and cAMP/Epac1/Rap1. These signaling merge at Rac1/cdc42 subsequently activate PAK1. Activated PAK1 enhances E-cadherin complex disruption and finally increases mESCs migration. |
| File Format | HTM / HTML |
| ISSN | 03636143 |
| e-ISSN | 15221563 |
| Journal | American Journal of Physiology - Cell Physiology |
| Issue Number | 5 |
| Volume Number | 298 |
| Language | English |
| Publisher | American Physiological Society |
| Publisher Date | 2010-05-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Discipline Cell Biology Embryonic Stem Cells Metabolism Guanine Nucleotide Exchange Factors Laminin Cdc42 Gtp-binding Protein Rac1 Gtp-binding Protein Rap1 Gtp-binding Proteins Animals Cell Movement Cyclic Amp Focal Adhesion Kinase 1 Integrin Alpha6beta1 Genetics Mice Paxillin Rna Interference Rna, Small Interfering Receptors, Laminin Signal Transduction Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Physiology |
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