Abstract
We compared the signal transduction pathways activated by stromal cell-derived factor-1 (CXCL12) chemokine in two different cell systems: primary cultures of rat cerebellar granule neurons (CGN) and human neuroepithelioma CHP100 cells. Both cell types express functional CXC chemokine receptor 4 (CXCR4), which is coupled both to extracellular signal-regulated kinase (ERK) and Akt phosphorylation pathways. The activation of ERK shows different dependency on the phosphatidylinositol 3-kinase (PI3-K) pathway and different sensitivity to pertussis toxin (PTX) treatment, indicative of coupling to different G proteins in the two cell systems considered. We demonstrate that the inhibition of either the ERK kinase or the PI3-K pathways blocks the CXCL12 induced-chemotaxis in CHP100 cells; while only PI3-K activity is stringently necessary for CGN migration.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Movement / drug effects
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Cells, Cultured
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Cerebellum / metabolism*
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Chemokine CXCL12
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Chemokines, CXC / pharmacology*
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Chemotactic Factors / pharmacology*
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Inositol 1,4,5-Trisphosphate / metabolism
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Mitogen-Activated Protein Kinases / metabolism
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Neuroectodermal Tumors, Primitive, Peripheral / metabolism*
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Pertussis Toxin / pharmacology
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Phosphatidylinositol 3-Kinases / physiology
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Phosphorylation
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Protein Serine-Threonine Kinases*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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Rats
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Rats, Wistar
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Signal Transduction*
Substances
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CXCL12 protein, human
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Chemokine CXCL12
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Chemokines, CXC
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Chemotactic Factors
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Proto-Oncogene Proteins
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Inositol 1,4,5-Trisphosphate
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Pertussis Toxin
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Akt1 protein, rat
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Mitogen-Activated Protein Kinases