Neurotrophic receptor tyrosine kinase B induces c-fos-associated cell survival.

ABSTRACT

The neurotrophic receptor tyrosine kinase B (TrkB) is a cell surface receptor for brain-derived neurotrophic factor (BDNF) with kinase activity. This protein is expressed in various tumors and thought to participate in various cellular processes. In this study, we established 293T cells stably expressing human TrkB to elucidate its intracellular functions. Using this cell system, we examined the biological roles of TrkB and its downstream target molecules. The TrkB expressing cells showed an increased survival rate through increased c-fos mRNA expression by BDNF, which were completely suppressed by TrkB inhibitor. Moreover, the combination of inhibitors of mitogen-activated protein kinase (MEK) and phosphatidylinositol 3-kinase (PI3K) partially reduced both the cell survival rate and c-fos mRNA expression, whereas monotreatment of these reagents could not affect cell survival nor c-fos mRNA expression. These results suggested that TrkB could play a role in c-fos-associated cell survival through both MEK and PI3K pathway. It is conceivable that activation of TrkB has a significant impact on tumorigenesis and metastasis.