A PTPome-wide Analysis of Drosophila Non-transmembrane Protein Tyrosine Phosphatases Unveils the Requirement of dHD-PTP in Development
Date Issued
2008
Date
2008
Author(s)
Chen, Dong-Yuan
Abstract
Protein tyrosine phosphatases (PTPs) are a group of tightly regulated enzymes in coordination with protein tyrosine kinases to control protein phosphorylation during various cellular processes. Accumulating evidence has indicated that regulation of tyrosine phosphorylation plays a crucial role during development. Drosophila PTPome is chosen as a model to define the developmental function of PTPs. Based on sequence similarity, fifteen putative PTPs in Drosophila genome are identified. Among them, seven of them are receptor like PTPs, and eight are predicted to be non-transmembrane PTPs. While much research has been devoted to the role of receptor-like tyrosine phosphatases in neural development, the function of non-transmembrane PTPs remains to be elucidated. o investigate the biological function of these non-transmembrane PTPs during development, I have systematically analyzed the gene expression pattern and phosphatase activity of these PTPs. Moreover, transgenic flies carrying wild type cDNA or double-stranded RNA of each non-transmembrane PTP were generated. in situ hybridization revealed that many of these PTPs are highly expressed in embryonic CNS and exhibited relatively low and ubiquitous expression in third instar larval imaginal discs. In addition, loss-of-function and gain-of function analysis revealed that dHD-PTP, a BRO1 domain containing protein tyrosine phosphatase, is required for wing morphogenesis. Immunofluorescence showed that dHD-PTP is localized at both early and late endosomes. Strikingly, both downregulation and overexpression of dHD-PTP affected the size of endosomes, suggesting a regulatory role of dHD-PTP in the biogenesis of endosomal structures. n addition, I found that overexpression of cyclinE, a gene known for it role in cell cycle progression, could partially rescue dHD-PTP loss-of-function defects in developing wing. This, along with the observation of ectopic cell death in dHD-PTP loss-of-function mosaic clones suggests possible involvements of dHD-PTP in cell proliferation and cell survival. Genetic analysis also found that dPax, a focal adhesion adaptor protein, genetically interacts with dHD-PTP during wing epithelia development.n summary, I demonstrate that dHD-PTP could function as an essential protein in regulation of endocytosis and cell adhesion during development. dHD-PTP might be involved in the control of cell adhesion by its ability to regulate the trafficking of adhesion-related molecules. Combined with characterization of other non-transmembrane PTPs, my studies should shed lights on the role of these non-transmembrane PTPs in development.
Subjects
Drosophila development
PTP
PTP-ome wide analysis
wing morphogenesis
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