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 Requena, Javier
A1 Meana González, Clara
A1 Esquinas, Esperanza
A1 Valdearcos, Martín
A1 Pindado, José
A1 Balsinde Rodríguez, Jesús
A1 Balboa García, María Ángeles
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 A2, also known as cytosolic phospholipase A2  (cPLA2 ). During phagocytosis, cPLA2  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 cPLA2  mutant (S505A) does not translocate to the phagosomes, but a mutant that mimics phosphorylation on Ser505 (S505E) does it so readily. During phagocytosis, endogenous cPLA2  is phosphorylated at Ser505, 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 cPLA2  to phagosomal membranes, as well as arachidonic acid release to the extracellular medium. Moreover, the S505E mutant makes the enzyme refractory to JNKinhibition, translocating normally to phagosomal membranes. Collectively, these data support a key role for JNK-mediated cPLA2  phosphorylation at Ser505 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/10324/74260
UL https://uvadoc.uva.es/handle/10324/74260
LA eng
NO Journal of Immunology, Agosto 2009, vol. 183, n. 4, p. 2767-2774
DS UVaDOC
RD 03-jun-2025