Signalling pathways involved in the chemotactic activity of CXCL12 in cultured rat cerebellar neurons and CHP100 neuroepithelioma cells.
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.
Floridi
Francesca
F
Dipartimento di Fisiologia Umana e Farmacologia, Università di Roma La Sapienza Piazzale Aldo Moro, 5, I-00185, Rome, Italy.
Trettel
Flavia
F
Di Bartolomeo
Sabrina
S
Ciotti
Maria Teresa
MT
Limatola
Cristina
C
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000378:metabolism*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology*; D002630:Chemotactic Factors / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018241:Neuroectodermal Tumors, Primitive, Peripheral / Q000378:metabolism*; D037342:Pertussis Toxin / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D015544:Inositol 1,4,5-Trisphosphate; D020928:Mitogen-Activated Protein Kinases; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C515255:CXCL12 protein, human; C494920:Akt1 protein, rat