HTK is a receptor tyrosine kinase that belongs to the Eph subfamily. An extensive screening using... more HTK is a receptor tyrosine kinase that belongs to the Eph subfamily. An extensive screening using BIAcore system revealed that a colon cancer cell line, C-1, expressed the ligand for HTK. From the conditioned medium of C-1 cells, a soluble form of ligand was purified by receptor affinity chromatography, and the isolation of full-length cDNA revealed that this ligand is identical to the human HTK ligand (HTKL) previously reported. HTK receptor tyrosine phosphorylation was induced by membrane-bound or clustered soluble HTKL but not by unclustered soluble HTKL, indicating that HTKL requires cell-to-cell interaction for receptor activation. Binding analysis demonstrated that HTKL binds to HTK with a much higher affinity (Kd: 1.23 nM) than the other transmembrane-type ligand for Eph family, LERK-2/ELKL (Kd: 135 nM). The expression of HTK in cord blood cells was upregulated after the culture in the presence of stem cell factor. Clustered soluble HTKL stimulated the proliferation of sorted HTK+ cord blood cells and a hematopoietic cell line, UT-7/EPO from which HTK was isolated. These findings suggest the involvement of HTK-HTKL system in the proliferation of HTK+ hematopoietic progenitor cells in the hematopoietic environment.
L'invention a trait a des acides amines constituant une molecule humaine active delta 2, a so... more L'invention a trait a des acides amines constituant une molecule humaine active delta 2, a son agencement genique et a un anticorps afferent. La molecule humaine delta 2, au moins la sequence aminoacide decrite dans SEQ ID N° 1 du listage des sequences, qui agit comme une substance chimique efficace en matiere de proliferation de cellules sanguines indifferenciees ainsi qu'en matiere d'inhibition de la differentiation, peut etre employee comme produit pharmaceutique et a usage medical.
We identified a novel non-receptor tyrosine kinase from a human megakaryoblastic cell line, UT-7,... more We identified a novel non-receptor tyrosine kinase from a human megakaryoblastic cell line, UT-7, by means of a PCR-based cloning method. The HYL gene contained a SH2 and SH3 domain and a tyrosine kinase catalytic domain. The deduced amino acid sequence of the protein encoded by this gene was most homologous to CSK (c-src kinase). This gene and CSK shared some unique structural properties such as the absence of a myristylation signal and phosphorylation sites of tyrosine residues corresponding to tyrosines 416 and 527 of chicken p60c-src. Unlike CSK, the SH3 domain of HYL was unique since the ALYDY motif was absent. Northern blot analysis revealed a 2.2 kb transcript in various myeloid cell lines but not in adult tissues except for the brain and the lung, whereas CSK mRNA was ubiquitously expressed. The expression of HYL was upregulated when these myeloid cells were differentiated by induction with phorbol myristate acetate. We named this gene, hematopoietic consensus tyrosine-lacki...
We identified a novel non-receptor tyrosine kinase from a human megakaryoblastic cell line, UT-7,... more We identified a novel non-receptor tyrosine kinase from a human megakaryoblastic cell line, UT-7, by means of a PCR-based cloning method. The HYL gene contained a SH2 and SH3 domain and a tyrosine kinase catalytic domain. The deduced amino acid sequence of the protein encoded by this gene was most homologous to CSK (c-src kinase). This gene and CSK shared some unique structural properties such as the absence of a myristylation signal and phosphorylation sites of tyrosine residues corresponding to tyrosines 416 and 527 of chicken p60c-src. Unlike CSK, the SH3 domain of HYL was unique since the ALYDY motif was absent. Northern blot analysis revealed a 2.2 kb transcript in various myeloid cell lines but not in adult tissues except for the brain and the lung, whereas CSK mRNA was ubiquitously expressed. The expression of HYL was upregulated when these myeloid cells were differentiated by induction with phorbol myristate acetate. We named this gene, hematopoietic consensus tyrosine-lacki...
Cette invention concerne un polypeptide contenant la sequence d'acide amine decrite dans le N... more Cette invention concerne un polypeptide contenant la sequence d'acide amine decrite dans le N° ID SEQ: 1 de la liste de sequences, et codee par un gene provenant d'un etre humain. Ce polypeptide peut etre utilise en qualite d'agent chimique efficace dans la suppression de la proliferation et la differenciation de cellules sanguines non differenciees, ce qui le rend utile dans des agents therapeutiques et des produits medicaux.
La presente invention concerne un ligand de tyrosine kinase de type recepteur se liant a la parti... more La presente invention concerne un ligand de tyrosine kinase de type recepteur se liant a la partie extracellulaire d'une tyrosine kinase specifiee de type recepteur et permettant d'accroitre l'activite enzymatique de la tyrosine kinase dans ladite partie intracellulaire afin d'induire la phosphorylation de la tyrosine kinase. Cette kinase specifiee en est une qui, d'une part, s'exprime dans des cellules sanguines indifferenciees, mais subit une baisse de niveau d'expression accompagnant la differenciation progressive des cellules sanguines, et d'autre part participe a la differenciation et a la croissance des cellules indifferenciees. L'invention concerne egalement un complexe constitue du ligand de la presente invention et de l'un au moins des elements appartenant a un groupe constitue du ligand et d'autres composes. L'invention concerne un ADN codant pour ce ligand. L'invention concerne ensuite un procede de production du ligand ...
Hajdu-Cheney syndrome (HCS), a rare autosomal disorder caused by heterozygous mutations in NOTCH2... more Hajdu-Cheney syndrome (HCS), a rare autosomal disorder caused by heterozygous mutations in NOTCH2, is clinically characterized by acro-osteolysis, severe osteoporosis, short stature, neurological symptoms, cardiovascular defects, and polycystic kidneys. Recent studies identified that aberrant NOTCH2 signaling and consequent osteoclast hyperactivity are closely associated with the bone-related disorder pathogenesis, but the exact molecular mechanisms remain unclear. Here, we demonstrate that sustained osteoclast activity is largely due to accumulation of NOTCH2 carrying a truncated C terminus that escapes FBW7-mediated ubiquitination and degradation. Mice with osteoclast-specific Fbw7 ablation revealed osteoporotic phenotypes reminiscent of HCS, due to elevated Notch2 signaling. Importantly, administration of Notch inhibitors in Fbw7 conditional knockout mice alleviated progressive bone resorption. These findings highlight the molecular basis of HCS pathogenesis and provide clinical ...
HTK is a receptor tyrosine kinase that belongs to the Eph subfamily. An extensive screening using... more HTK is a receptor tyrosine kinase that belongs to the Eph subfamily. An extensive screening using BIAcore system revealed that a colon cancer cell line, C-1, expressed the ligand for HTK. From the conditioned medium of C-1 cells, a soluble form of ligand was purified by receptor affinity chromatography, and the isolation of full-length cDNA revealed that this ligand is identical to the human HTK ligand (HTKL) previously reported. HTK receptor tyrosine phosphorylation was induced by membrane-bound or clustered soluble HTKL but not by unclustered soluble HTKL, indicating that HTKL requires cell-to-cell interaction for receptor activation. Binding analysis demonstrated that HTKL binds to HTK with a much higher affinity (Kd: 1.23 nM) than the other transmembrane-type ligand for Eph family, LERK-2/ELKL (Kd: 135 nM). The expression of HTK in cord blood cells was upregulated after the culture in the presence of stem cell factor. Clustered soluble HTKL stimulated the proliferation of sorted HTK+ cord blood cells and a hematopoietic cell line, UT-7/EPO from which HTK was isolated. These findings suggest the involvement of HTK-HTKL system in the proliferation of HTK+ hematopoietic progenitor cells in the hematopoietic environment.
L'invention a trait a des acides amines constituant une molecule humaine active delta 2, a so... more L'invention a trait a des acides amines constituant une molecule humaine active delta 2, a son agencement genique et a un anticorps afferent. La molecule humaine delta 2, au moins la sequence aminoacide decrite dans SEQ ID N° 1 du listage des sequences, qui agit comme une substance chimique efficace en matiere de proliferation de cellules sanguines indifferenciees ainsi qu'en matiere d'inhibition de la differentiation, peut etre employee comme produit pharmaceutique et a usage medical.
We identified a novel non-receptor tyrosine kinase from a human megakaryoblastic cell line, UT-7,... more We identified a novel non-receptor tyrosine kinase from a human megakaryoblastic cell line, UT-7, by means of a PCR-based cloning method. The HYL gene contained a SH2 and SH3 domain and a tyrosine kinase catalytic domain. The deduced amino acid sequence of the protein encoded by this gene was most homologous to CSK (c-src kinase). This gene and CSK shared some unique structural properties such as the absence of a myristylation signal and phosphorylation sites of tyrosine residues corresponding to tyrosines 416 and 527 of chicken p60c-src. Unlike CSK, the SH3 domain of HYL was unique since the ALYDY motif was absent. Northern blot analysis revealed a 2.2 kb transcript in various myeloid cell lines but not in adult tissues except for the brain and the lung, whereas CSK mRNA was ubiquitously expressed. The expression of HYL was upregulated when these myeloid cells were differentiated by induction with phorbol myristate acetate. We named this gene, hematopoietic consensus tyrosine-lacki...
We identified a novel non-receptor tyrosine kinase from a human megakaryoblastic cell line, UT-7,... more We identified a novel non-receptor tyrosine kinase from a human megakaryoblastic cell line, UT-7, by means of a PCR-based cloning method. The HYL gene contained a SH2 and SH3 domain and a tyrosine kinase catalytic domain. The deduced amino acid sequence of the protein encoded by this gene was most homologous to CSK (c-src kinase). This gene and CSK shared some unique structural properties such as the absence of a myristylation signal and phosphorylation sites of tyrosine residues corresponding to tyrosines 416 and 527 of chicken p60c-src. Unlike CSK, the SH3 domain of HYL was unique since the ALYDY motif was absent. Northern blot analysis revealed a 2.2 kb transcript in various myeloid cell lines but not in adult tissues except for the brain and the lung, whereas CSK mRNA was ubiquitously expressed. The expression of HYL was upregulated when these myeloid cells were differentiated by induction with phorbol myristate acetate. We named this gene, hematopoietic consensus tyrosine-lacki...
Cette invention concerne un polypeptide contenant la sequence d'acide amine decrite dans le N... more Cette invention concerne un polypeptide contenant la sequence d'acide amine decrite dans le N° ID SEQ: 1 de la liste de sequences, et codee par un gene provenant d'un etre humain. Ce polypeptide peut etre utilise en qualite d'agent chimique efficace dans la suppression de la proliferation et la differenciation de cellules sanguines non differenciees, ce qui le rend utile dans des agents therapeutiques et des produits medicaux.
La presente invention concerne un ligand de tyrosine kinase de type recepteur se liant a la parti... more La presente invention concerne un ligand de tyrosine kinase de type recepteur se liant a la partie extracellulaire d'une tyrosine kinase specifiee de type recepteur et permettant d'accroitre l'activite enzymatique de la tyrosine kinase dans ladite partie intracellulaire afin d'induire la phosphorylation de la tyrosine kinase. Cette kinase specifiee en est une qui, d'une part, s'exprime dans des cellules sanguines indifferenciees, mais subit une baisse de niveau d'expression accompagnant la differenciation progressive des cellules sanguines, et d'autre part participe a la differenciation et a la croissance des cellules indifferenciees. L'invention concerne egalement un complexe constitue du ligand de la presente invention et de l'un au moins des elements appartenant a un groupe constitue du ligand et d'autres composes. L'invention concerne un ADN codant pour ce ligand. L'invention concerne ensuite un procede de production du ligand ...
Hajdu-Cheney syndrome (HCS), a rare autosomal disorder caused by heterozygous mutations in NOTCH2... more Hajdu-Cheney syndrome (HCS), a rare autosomal disorder caused by heterozygous mutations in NOTCH2, is clinically characterized by acro-osteolysis, severe osteoporosis, short stature, neurological symptoms, cardiovascular defects, and polycystic kidneys. Recent studies identified that aberrant NOTCH2 signaling and consequent osteoclast hyperactivity are closely associated with the bone-related disorder pathogenesis, but the exact molecular mechanisms remain unclear. Here, we demonstrate that sustained osteoclast activity is largely due to accumulation of NOTCH2 carrying a truncated C terminus that escapes FBW7-mediated ubiquitination and degradation. Mice with osteoclast-specific Fbw7 ablation revealed osteoporotic phenotypes reminiscent of HCS, due to elevated Notch2 signaling. Importantly, administration of Notch inhibitors in Fbw7 conditional knockout mice alleviated progressive bone resorption. These findings highlight the molecular basis of HCS pathogenesis and provide clinical ...
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