c-Jun N-terminal kinase controls a negative loop in the regulation of glial fibrillary acidic protein expression by retinoic acid.

[alexander disease]

Glial fibrillary acidic protein (GFAP ) is a protein widely used as a molecular marker for astroglial differentiation and mature astrocytes . We and others have shown previously that retinoic acid and specific cytokines induce the expression of GFAP in neural precursor cells by activating the phosphatidylinositol-4 ,5 -bisphosphate-3 -kinase (PI 3 K ) phosphorylation pathway . Here , we extend our previous work and show that retinoic acid also activates specifically the c-Jun N-terminal kinase (JNK ) phosphorylation pathway , which in turn inhibits GFAP expression . Our results suggest the existence of a negative self-regulatory loop in the phosphorylation pathways that regulates GFAP expression . This loop is constitutively repressed by the PI 3 K pathway . Our results could be relevant for disorders involving sustained GFAP overexpression in precursor cells , such as glioblastoma and Alexander disease .