Sumiko Watanabe 교수

Interleukin-3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to activate JAK2 in various cells, but the role of JAK2 in IL-3 or GM-CSF receptor signal transduction is largely unknown. We have now examined the role of JAK2 in GM-CSF-induced signaling events in BA/F3 cells. In BA/F3 cells expressing hGMR, activation of JAK2 by hGM-CSF requires the box1 region of hGMR beta. Dominant negative JAK2 (delta JAK2), which lacked the kinase domain suppressed mIL-3 or hGM-CSF-

Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays a critical role in growth and differentiation of myeloid cells. We previously reconstituted high-affinity human GM-CSF receptor (hGM-CSFR) in a pro-B cell line, BA/F3, by cotransfecting alpha- and beta-chain cDNA clones and showed that the reconstituted receptor could transduce growth-promoting signals. The high-affinity hGM-CSFR was also reconstituted in mouse NIH 3T3 cells, but its ability to transduce signals in fibroblasts remai

CD73 is a cell surface marker of cone/rod common precursors and mature rod cells in mice and is genetically localized between Nrl and Crx. The expression of CD73 was conserved in primate rod cells, and CD73 provides an useful tool to purify photoreceptor cells for transplantation aimed at the regeneration of photoreceptors.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) induces various functions, including the proliferation and differentiation of a broad range of hematopoietic cells. We previously reported that at least two distinct pathways are involved in human GM-CSF receptor signaling; both require the box 1 region of the common beta subunit (beta c). This region is essential for the activation of JAK2, which is necessary for all the biological functions of GM-CSF. The activation of JAK2 by GM-CSF le

The histone modification H3K27me3 regulates transcription negatively, and Jmjd3 and Ezh2 demethylate and methylate H3K27me3 and H3K27, respectively. We demonstrated previously that Jmjd3 plays pivotal roles in the differentiation of subsets of bipolar (BP) cells by regulating H3K27me3 levels at the Bhlhb4 and Vsx1 loci, both of which are transcription factors essential for the maturation of BP cell subsets. In this study, we examined the role of Ezh2 in retinal development using retina-specific

The discovery that bile canaliculi are capable of spontaneous contractile activity has led to their use in the investigation of the physiology of the liver cell. The contraction of a bile canaliculus is dependent on the network of actin, which is found in the pericanalicular region of the hepatocyte, and agents that inhibit actin filaments interfere with canalicular contraction. Injection of calcium directly into the cytoplasm of one hepatocyte of a cell pair results in contraction. Injection of

Medulloblastoma is the most common pediatric brain tumor, and in ∼25% of cases, it is driven by aberrant activation of the Sonic Hedgehog (SHH) pathway in granule neuron precursor (GNP) cells. In this study, we identified novel medulloblastoma driver genes through a transposon mutagenesis screen in the developing brain of wild-type and Trp53 mutant mice. Twenty-six candidates were identified along with established driver genes such as Gli1 and Crebbp. The transcription factor FoxR2, the most fre

Neurodegeneration has been shown to induce microglial activation and the infiltration of monocyte-derived macrophages into the CNS, resulting in the coexistence of these two populations within the same lesion, though their distinct features remain elusive. To investigate the impact of rod photoreceptor degeneration on microglial activation, we generated a toxin-mediated genetic model of rod degeneration. Rod injury induced microglial proliferation and migration toward the photoreceptors. Bone ma

Granulocyte macrophage colony-stimulating factor (GM-CSF) binds to the high-affinity GM-CSF receptor (GMR) consisting of alpha and beta subunits and induces rapid tyrosine phosphorylation, activation of early response genes, and proliferation of hematopoietic cells. The alpha subunit is the primary cytokine binding component and the beta subunit is required for high-affinity binding as well as for signal transduction. Using tyrosine kinase inhibitors and cytoplasmic deletion mutants of the beta

The effects of prostaglandin E2 (PGE2) on cytokine production and proliferation of the CD4+ human helper T cell clone SP-B21 were investigated. In cells stimulated with anti-CD3 mAb, PGE2 inhibited cell proliferation and the production of all the cytokines examined. Addition of rIL-2 fully restored the proliferative response and partially restored the production of IL-4 and IL-5, but not that of other cytokines. In contrast, in cells stimulated with phorbol myristate acetate (PMA)/A23187, PGE2 e