Elevated levels of growth-promoting receptors on the cell surface can contribute to oncogenesis and resistance to targeted therapy. We have found that the tyrosine phosphatase PTPN14 (also called Pez) limits the recycling of endocytosed receptors back to the cell surface. We have now identified the key substrate of PTPN14, PKCδ (Belle et al, 2015), that regulates receptor recycling and the upstream tyrosine kinase (TK) that phosphorylates PKCδ. In this pathway, the substrate PKCδ when phosphorylated on Y374 limits trafficking to lysosomes and promotes recycling. This role of PTPN14 is consistent with the finding that PTPN14 is mutated in a proportion of breast and other cancers. Data will be presented on the role of the PTPN14-PKCδ-TK axis, receptor recycling and the activation of multiple RTKs in triple negative breast cancer (TNBC). We will also present data on a new PTPN14 knock-out mouse, which has elevated pY374-PKCδ levels. This mouse has defects, including hyperplasia and loss of polarity, in the epithelia of multiple organs.
Ref: Belle L et al (2015) Sci Signaling 33:ra18