RT info:eu-repo/semantics/article
T1 Requirement of JNK-Mediated Phosphorylation for Translocation of Group IVA Phospholipase A2 to Phagosomes in Human Macrophages
A1 Casas, Javier
A1 Meana, Clara
A1 Esquinas, Esperanza
A1 Valdearcos, Martín
A1 Pindado, José
A1 Balsinde, Jesús
A1 Balboa, María A.
AB Eicosanoids are a broad family of lipids that play a critical role in host defense against bacterial and fungal infections. The first enzyme in the metabolic pathway for the generation of eicosanoids is group IVA phospholipase A(2), also known as cytosolic phospholipase A(2)alpha (cPLA(2)alpha). During phagocytosis, cPLA(2)alpha has been found to translocate to the phagosome, although the molecular mechanism involved in such a translocation has not been elucidated. By using enhanced GFP-tagged proteins we show in this work that a nonphosphorylatable cPLA(2)alpha mutant (S505A) does not translocate to the phagosomes, but a mutant that mimics phosphorylation on Ser(505) (S505E) does it so readily. During phagocytosis, endogenous cPLA(2)alpha is phosphorylated at Ser(505), and inhibitors of JNK, but not of other related kinases such as p38 or the extracellular-regulated kinases 1 and 2, completely block such a phosphorylation. Inhibition of JNK activity also inhibits the translocation of cPLA(2)alpha to phagosomal membranes, as well as arachidonic acid release to the extracellular medium. Moreover, the S505E mutant makes the enzyme refractory to JNK inhibition, translocating normally to phagosomal membranes. Collectively, these data support a key role for JNK-mediated cPLA(2)alpha phosphorylation at Ser(505) in the sequence of events leading to translocation and activation of the enzyme to phagosomal membranes in human macrophages
SN 0022-1767
YR 2009
FD 2009
LK https://uvadoc.uva.es/handle/10324/64294
UL https://uvadoc.uva.es/handle/10324/64294
LA eng
NO The Journal of Immunology 183, 2767–2774 (2009).
NO Producción Científica
DS UVaDOC
RD 19-nov-2024