Role of protein tyrosine phosphatases in organelle biogenesis

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The proposed research program is aimed at understanding the role(s) of protein tyrosine phosphatases in the biogenesis of phagolysosomes, a model organelle. Phagolysosome biogenesis requires the coordinated action of multiple signaling molecules, including several protein kinases, which regulate the interactions between the phagosome and the cytoskeleton, as well as the early, late and recycling endocytic compartments. A recent large scale quantitative proteomic and phosphoproteomic analyses revealed that tyrosine (Tyr) phosphorylation sites are overrepresented in phagosomes, as compared to global phosphoproteome. This finding suggests that Tyr phosphorylation plays an important role in phagosome signaling. Appropriate control of protein tyrosine phosphorylation is essential for cellular homeostasis, and this is achieved by the balanced action of protein tyrosine kinases (PTKs) and PTPs. The role of PTPs in organelle biogenesis in general and in the control of phagolysosome biogenesis in particular, is largely unknown. Our general hypothesis is that PTPs participate in the biogenesis of phagolysosomes. To address this hypothesis, we propose the following Objectives.