Protein tyrosine kinase 7 promotes PI3K/AKT signaling and survival in primary and neoplastic CD4+ T-lineage cells. (HEM4P.231)

Abstract

Abstract Protein tyrosine kinase 7 (PTK7), a catalytically inactive receptor tyrosine kinase (RTK) that is highly expressed in intrathymic development, is a novel marker for human CD4+ recent thymic emigrants (RTEs), and is also highly expressed on some T-lineage thymomas, e.g., Jurkat cells. The function of PTK7 in normal human T-cell development and tumors remains unclear. Here, using RNAi-mediated gene silencing in T-lineage tumor cells, primary human peripheral T-cells and thymocytes, we found that targeting PTK7 consistently decreased cell survival by augmenting caspase-3 activation of apoptosis. The PTK7 knockdown also decreased AKT phosphorylation and PI3 kinase activity, suggesting an essential role for PTK7 in survival of RTEs and developing thymocytes involving the PI3K/AKT pathway. Using mass spectrometry of we identified insulin-like growth factor-1 (IGF-1) receptor as an active kinase partner of PTK7. Knockdown of PTK7 reduced IGF-1 receptor function in primary T-lineage cells, confirming the biologic importance of this physical association. This role for PTK7 in promoting cell survival via its effects on cell survival via the PI3K/AKT pathway may not only be relevant to normal T-cell development, including the RTE compartment, but also to the oncogenesis of T-lineage and epithelial cell tumors.