Cell signaling pathways to alphaB-crystallin following stresses of the cytoskeleton.
Small heat shock proteins (sHSPs) act as chaperone, but also in protecting the different cytoskeletal components. Recent results suggest that alphaB-crystallin, a member of sHSPs family, might regulate actin filament dynamics, stabilize them in a phosphorylation dependent manner, and protect the integrity of intermediate filaments (IF) against extracellular stress. We demonstrate that vinblastin and cytochalasin D, which respectively disorganize microtubules and actin microfilaments, trigger the activation of the p38/MAPKAP2 kinase pathway and lead to the specific alphaB-crystallin phosphorylation at serine 59. Upstream of p38, we found that RhoK, PKC and PKA are selectively involved in the activation of p38 and phosphorylation of alphaB-crystallin, depending on the cytoskeletal network disorganized. Moreover, we demonstrate that chronic perturbations of IF network result in the same activation of p38 MAPK and alphaB-crystallin phosphorylation, as with severe disorganization of other cytoskeletal networks. Finally, we also show that Ser 59 phosphorylated alphaB-crystallin colocalizes with cytoskeletal components. Thus, disturbance of cytoskeleton leads by converging signaling pathways to the phosphorylation of alphaB-crystallin, which probably acts as a protective effector of the cytoskeleton.
Launay
Nathalie
N
EA 300 Stress et Pathologies du Cytosquelette, UFR de Biochimie, Université Paris 7, 2 place Jussieu, 75005 Paris, France.
Goudeau
Bertrand
B
Kato
Kanefusa
K
Vicart
Patrick
P
Lilienbaum
Alain
A
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D003893:Desmin / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D051606:G-Protein-Coupled Receptor Kinase 1 / Q000378:metabolism; D007382:Intermediate Filaments / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D018384:Oxidative Stress; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D050257:Tubulin Modulators / Q000494:pharmacology; D014747:Vinblastine / Q000494:pharmacology; D016596:Vinculin / Q000378:metabolism; D038203:alpha-Crystallin B Chain / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000099190:MAP-Kinase-Activated Kinase 2
D000199:Actins; D017868:Cyclic AMP-Dependent Protein Kinases; D015638:Cytochalasin D; D003893:Desmin; D004791:Enzyme Inhibitors; D051606:G-Protein-Coupled Receptor Kinase 1; D047908:Intracellular Signaling Peptides and Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D011493:Protein Kinase C; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D012694:Serine; D050257:Tubulin Modulators; D014747:Vinblastine; D016596:Vinculin; D038203:alpha-Crystallin B Chain; D048051:p38 Mitogen-Activated Protein Kinases; D000099190:MAP-Kinase-Activated Kinase 2; C098416:MAP-kinase-activated kinase 3; C496762:Grk1 protein, mouse