Kettering University

About: Kettering University is a education organization based out in Flint, Michigan, United States. It is known for research contribution in the topics: Cancer & RNA. The organization has 6842 authors who have published 7689 publications receiving 337503 citations. The organization is also known as: GMI Engineering & Management Institute & General Motors Institute.

Interaction of the erythropoietin and stem-cell-factor receptors

Abstract: MUTATIONS in the KIT transmembrane protein-tyrosine kinase receptor1 affect erythropoiesis, resulting in fewer committed late progenitors (colony-forming unit erythroid, CFU-E) in the fetal liver2. As the survival and proliferation of CFU-Es depend absolutely on erythropoietin (EPO)3, these results suggest that CFU-Es cannot proliferate or mature further unless both the KIT and EPO receptor4 signalling pathways are functional. How KIT affects proliferation or differentiation of CFU-Es is not clear. Here we show that the KIT ligand SCF (for stem-cell factor) can replace EPO in supporting the growth and survival of HCD57 cells, an EPO-dependent erythroid-progenitor cell line expressing high levels of KIT5. SCF supports the proliferation of 32D cells6 that express KIT only if they also express the EPO receptor. In HCD57 cells, SCF rapidly induces tyrosine phosphorylation of the EPO receptor, and KIT physically associates with the extended box 2 region7 in the cytoplasmic domain of the EPO receptor. Our results indi-cate that KIT may activate the EPO receptor by tyrosine phosphorylation to induce further proliferation and maturation of CFU-Es.

Protein Folding in the Cell: The Role of Molecular Chaperones Hsp70 and Hsp60

Abstract: THE MEMBERS OFTHE HSP70 FAMILY •• 298 Unfolding Is Required for Membrane Translocation of Proteins 299 Cytoso/ic Hsp70 Stabilizes Precursor Proteins for Translocation 300 Organellar Hsp70 in Protein Translocation and Folding 301 Requirement of Hsp70 for Protein Assembly in the ER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 302 Molecular Mechanism of Hsp70 Action .... .. . . . . . . . . . .. . .. . . .. ... . . . ........ 303 THE MEMBERS OF THE HSP60 FAMILY ... ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . 306 Multiple Functions of Mitochondrial Hsp60 308 Molecular Mechanism of Chaperon in Action . .. . . . 311

Mouse Kif7/Costal2 is a cilia-associated protein that regulates Sonic hedgehog signaling

Abstract: Mammalian Sonic hedgehog (Shh) signaling is essential for embryonic development and stem cell maintenance and has critical roles in tumorigenesis. Although core components of the Shh pathway are conserved in evolution, important aspects of mammalian Shh signaling are not shared with the Drosophila pathway. Perhaps the most dramatic difference between the Drosophila and mammalian pathways is that Shh signaling in the mouse requires a microtubule-based organelle, the primary cilium. Proteins that are required for the response to Shh are enriched in the cilium, but it is not clear why the cilium provides an appropriate venue for signal transduction. Here, we demonstrate that Kif7, a mammalian homologue of Drosophila Costal2 (Cos2), is a cilia-associated protein that regulates signaling from the membrane protein Smoothened (Smo) to Gli transcription factors. By using a Kif7 mutant allele identified in a reporter-based genetic screen, we show that, similar to Drosophila and zebrafish Cos2, mouse Kif7 acts downstream of Smo and upstream of Gli2 and has both negative and positive roles in Shh signal transduction. Mouse Kif7 activity depends on the presence of cilia and Kif7-eGFP localizes to base of the primary cilium in the absence of Shh. Activation of the Shh pathway promotes trafficking of Kif7-eGFP from the base to the tip of the cilium, and localization to the tip of the cilium is disrupted in a motor domain mutant. We conclude that Kif7 is a core regulator of Shh signaling that may also act as a ciliary motor.