Crosstalk between p38, Hsp25 and Akt in spinal motor neurons after sciatic nerve injury.
The p38 stress-activated protein kinase pathway is involved in regulation of phosphorylation of Hsp25, which in turn regulates actin filament dynamic in non-neuronal cells. We report that p38, Hsp25 and Akt signaling pathways were specifically activated in spinal motor neurons after sciatic nerve axotomy. The activation of the p38 kinase was required for induction of Hsp25 expression. Furthermore, Hsp25 formed a complex with Akt, a member of PI-3 kinase pathway that prevents neuronal cell death. Together, our observations implicate Hsp25 as a central player in a complex system of signaling that may both promote regeneration of nerve fibers and prevent neuronal cell death in the injured spinal cord.
Murashov
A K
AK
Department of Physiology, The Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA. murashoval@mail.ecu.edu
Haq
I U
IU
Hill
C
C
Park
E
E
Smith
M
M
Wang
X
X
Wang
X
X
Goldberg
D J
DJ
Wolgemuth
D J
DJ
D000818:Animals; D019771:Axotomy; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006360:Heat-Shock Proteins; D007093:Imidazoles / Q000494:pharmacology; D008161:Lumbosacral Region; D020935:MAP Kinase Signaling System; D046911:Macromolecular Substances; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D008959:Models, Neurological; D018832:Molecular Chaperones; D009046:Motor Neurons / Q000502:physiology*; D009363:Neoplasm Proteins / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D011725:Pyridines / Q000494:pharmacology; D020239:Receptor Cross-Talk; D012584:Sciatic Nerve / Q000293:injuries*; D013116:Spinal Cord / Q000473:pathology* / Q000503:physiopathology; D013312:Stress, Physiological / Q000502:physiology; D014403:Tubocurarine / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D006360:Heat-Shock Proteins; C486113:Hsbp1 protein, mouse; D007093:Imidazoles; D046911:Macromolecular Substances; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D011725:Pyridines; D009538:Nicotine; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; D014403:Tubocurarine