Author
Yasuhiro Moriyama
Bio: Yasuhiro Moriyama is an academic researcher from Osaka University. The author has contributed to research in topics: Receptor tyrosine kinase & Stem cell factor. The author has an hindex of 10, co-authored 13 publications receiving 4888 citations.
Papers
More filters
TL;DR: Sequencing of c-kit complementary DNA from five GISTs revealed mutations in the region between the transmembrane and tyrosine kinase domains, suggesting that the mutations contribute to tumor development.
Abstract: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the human digestive tract, but their molecular etiology and cellular origin are unknown. Sequencing of c-kit complementary DNA, which encodes a proto-oncogenic receptor tyrosine kinase (KIT), from five GISTs revealed mutations in the region between the transmembrane and tyrosine kinase domains. All of the corresponding mutant KIT proteins were constitutively activated without the KIT ligand, stem cell factor (SCF). Stable transfection of the mutant c-kit complementary DNAs induced malignant transformation of Ba/F3 murine lymphoid cells, suggesting that the mutations contribute to tumor development. GISTs may originate from the interstitial cells of Cajal (ICCs) because the development of ICCs is dependent on the SCF-KIT interaction and because, like GISTs, these cells express both KIT and CD34.
4,311 citations
TL;DR: The involvement of (+)-MITF in the c-kit transactivation appeared to be specific to the mast cell lineage.
173 citations
TL;DR: Proteoliposomes reconstituted with F0F1 and solubilized transporters from chromaffin granules or synaptic vesicle membranes could transport serotonin, dopamine, and norepinephrine dependent on ATP hydrolysis.
120 citations
TL;DR: The deletion of seven amino acids at the juxtamembrane domain appeared to be a new activating mutation of KIT that might be involved in neoplastic growth of mast cells.
114 citations
TL;DR: Results suggested that c-mpl may be functional in terms of supporting proliferation of various types of AML cells and that TPO may contribute, at least in part, to abnormal growth of the cells, especially in combination with other hematopoietic growth factors.
96 citations
Cited by
More filters
TL;DR: Sequencing of c-kit complementary DNA from five GISTs revealed mutations in the region between the transmembrane and tyrosine kinase domains, suggesting that the mutations contribute to tumor development.
Abstract: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the human digestive tract, but their molecular etiology and cellular origin are unknown. Sequencing of c-kit complementary DNA, which encodes a proto-oncogenic receptor tyrosine kinase (KIT), from five GISTs revealed mutations in the region between the transmembrane and tyrosine kinase domains. All of the corresponding mutant KIT proteins were constitutively activated without the KIT ligand, stem cell factor (SCF). Stable transfection of the mutant c-kit complementary DNAs induced malignant transformation of Ba/F3 murine lymphoid cells, suggesting that the mutations contribute to tumor development. GISTs may originate from the interstitial cells of Cajal (ICCs) because the development of ICCs is dependent on the SCF-KIT interaction and because, like GISTs, these cells express both KIT and CD34.
4,311 citations
TL;DR: How oncogenic conversion of protein kinases results from perturbation of the normal autoinhibitory constraints on kinase activity is emphasized and an update is provided on the role of deregulated PI(3)K/Akt and mammalian target of rapamycin/p70S6K signalling in human malignancies.
Abstract: Protein-tyrosine kinases (PTKs) are important regulators of intracellular signal-transduction pathways mediating development and multicellular communication in metazoans Their activity is normally tightly controlled and regulated Perturbation of PTK signalling by mutations and other genetic alterations results in deregulated kinase activity and malignant transformation The lipid kinase phosphoinositide 3-OH kinase (PI(3)K) and some of its downstream targets, such as the protein-serine/threonine kinases Akt and p70 S6 kinase (p70S6K), are crucial effectors in oncogenic PTK signalling This review emphasizes how oncogenic conversion of protein kinases results from perturbation of the normal autoinhibitory constraints on kinase activity and provides an update on our knowledge about the role of deregulated PI(3)K/Akt and mammalian target of rapamycin/p70S6K signalling in human malignancies
3,691 citations
TL;DR: Key elements of the consensus are the defining role of KIT immunopositivity in diagnosis and a proposed scheme for estimating metastatic risk in these lesions, based on tumor size and mitotic count, recognizing that it is probably unwise to use the definitive term "benign" for any GIST, at least at the present time.
3,326 citations
TL;DR: A 'census' of cancer genes is conducted that indicates that mutations in more than 1% of genes contribute to human cancer.
Abstract: A central aim of cancer research has been to identify the mutated genes that are causally implicated in oncogenesis ('cancer genes'). After two decades of searching, how many have been identified and how do they compare to the complete gene set that has been revealed by the human genome sequence? We have conducted a 'census' of cancer genes that indicates that mutations in more than 1% of genes contribute to human cancer. The census illustrates striking features in the types of sequence alteration, cancer classes in which oncogenic mutations have been identified and protein domains that are encoded by cancer genes.
3,136 citations
TL;DR: Tumor size predicts disease-specific survival in patients with primary disease who undergo complete gross resection and investigational protocols are indicated to reduce the rate of recurrence after resections and to improve the outcome for patients with GIST.
Abstract: ObjectiveTo analyze the outcome of 200 patients with gastrointestinal stromal tumor (GIST) who were treated at a single institution and followed up prospectively.Summary Background DataA GIST is a visceral sarcoma that arises from the gastrointestinal tract. Surgical resection is the mainstay of tre
2,532 citations