Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

TEK, or TIE-2, is a receptor tyrosine kinase (RTK) that is known as a functioning molecule of vascular endothelial cells. TEK comprises a subfamily of RTK with TIE, and these two receptors play critical roles in vascular maturation, maintenance of integrity and remodeling. We generated mAb against the extracellular domain of human TEK protein to elucidate its expression pattern in human hematopoietic cells. Flow cytometric analysis of bone marrow cells revealed that TEK was expressed in 27% of CD34+ cells, 20% of c-KIT+ cells and 26% of CD34+CD38- cells, indicating that TEK is expressed in a subset of primitive hematopoietic stem cells (HSC). TEK was also expressed in 20% of CD19+ B lymphocytes but not in other lineage-committed cells. Progenitor assays in methylcellulose culture showed that CD34+TEK+ cells formed significantly less BFU-E and CFU-Mix than CD34+TEK- cells, but there was no difference in the number of CFU-GM between these two populations. Two recently identified TEK ligands, termed Angiopoietin-1 and -2, bound to TEK with similar affinities, and Angiopoietin-1 effectively induced TEK phosphorylation in hematopoietic cells. Angiopoietin-2 also induced a low level of TEK phosphorylation and weakened the phosphorylation induced by Angiopoietin-1, suggestive of an elaborate regulator of the TEK-TEK ligand signaling pathway. Although neither ligands affected the proliferation of TEK-transfected hematopoietic cells or the colony formation of CD34+TEK+ bone marrow cells, both promoted the adhesion of TEK-transfected hematopoietic cells to a collagen matrix or a layer of bone marrow stromal cells. These findings indicate that the TEK-TEK ligand signaling pathway is regulated in a refined manner and is involved in hematopoietic cell-microenvironment interaction.
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PMID:Characterization of TEK receptor tyrosine kinase and its ligands, Angiopoietins, in human hematopoietic progenitor cells. 972 9

Hemodialized pediatric patients are a risk population for the hepatitis B and C virus infection. The aim of this paper was to study the serum prevalence of HBV and HCV infection in hemodialized children. We study 61 pediatric patients at hemodialisis, 12 on renal transplant, range between 2 and 20 years old (mean: 12.9 years), 23 male and 38 female. The specific anti-HCV IgC were measured by enzyme immunoassay (ELISA Abbott) and confirmed by LIA-TEK (Organon). The anti-HBV were measured by ELISA Abbott and transaminases by cinetic method (ASAT: 29 UI/L and ALT: 33 UI/L). The 19.7% of studied children were HCV (+) and 29.5% were HBV (+), 38.9% of them were HbsAg (+) and 50% anti-HBs (+). The HCV and HBV infection was more elevated in relation to the transfusion number and the hemodilisis time. The elevation of ALT/ASAT activity isn't a right infection index for HCV and HBV in this children.
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PMID:[HCV and HBV prevalence in hemodialyzed pediatric patients. Multicenter study]. 977 56

We have investigated the function of TIE2/TEK receptor tyrosine kinase in the development of definitive hematopoiesis. In the vitelline artery at 9.5 days postcoitum (d.p.c.), TIE2+ hematopoietic cells aggregated and adhered to TIE2+ endothelial cells. Soluble TIE2-Fc chimeric protein inhibited the development of hematopoiesis and angiogenesis in the para-aortic splanchnopleural mesoderm (P-Sp) explant culture, and TIE2-deficient mice showed severely impaired definitive hematopoiesis. An in vitro study revealed that Angiopoietin-1 but not Angiopoietin-2 promoted the adhesion to fibronectin (FN) through integrins in TIE2-transfected cells and primary TIE2+ cells sorted from 9.5 d.p.c. P-Sp. Adhesion of TIE2+ cells induced by Angiopoietin-1 enhanced the proliferation of hematopoietic progenitor cells.
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PMID:Critical role of the TIE2 endothelial cell receptor in the development of definitive hematopoiesis. 984 89

Recent studies have shown that long-term repopulating hematopoietic stem cells (HSCs) first appear in the aorta-gonad-mesonephros (AGM) region. Our immunohistochemistry study showed that TEK+ cells existed in the AGM region. Approximately 5% of AGM cells were TEK+, and most of these were CD34(+) and c-Kit+. We then established a coculture system of AGM cells using a stromal cell line, OP9, which is deficient in macrophage colony-stimulating factor (M-CSF). With this system, we showed that AGM cells at 10.5 days postcoitum (dpc) differentiated and proliferated into both hematopoietic and endothelial cells. Proliferating hematopoietic cells contained a significant number of colony-forming cells in culture (CFU-C) and in spleen (CFU-S). Among primary AGM cells at 10.5 dpc, sorted TEK+ AGM cells generated hematopoietic cells and platelet endothelial cell adhesion molecule (PECAM)-1(+) endothelial cells on the OP9 stromal layer, while TEK- cells did not. When a ligand for TEK, angiopoietin-1, was added to the single-cell culture of AGM, endothelial cell growth was detected in the wells where hematopoietic colonies grew. Although the incidence was still low (1/135), we showed that single TEK+ cells generated hematopoietic cells and endothelial cells simultaneously, using a single-cell deposition system. This in vitro coculture system shows that the TEK+ fraction of primary AGM cells is a candidate for hemangioblasts, which can differentiate into both hematopoietic cells and endothelial cells.
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PMID:In vitro hematopoietic and endothelial cell development from cells expressing TEK receptor in murine aorta-gonad-mesonephros region. 1002 83

The purpose of this report is to demonstrate the expression of very recently identified surface antigens on CD34+ and AC133+ bone marrow (BM) cells. Coexpression analysis of AC133 and defined antigens on CD34+ BM cells revealed that the majority of the CD164+, CD135+, CD117+, CD38low, CD33+, and CD71low cells resides in the AC133+ population. In contrast, most of the CD10+ and CD19+ B cell progenitors and a fraction of the CD71high population are AC133-, indicating that CD34+AC133+ cells are enriched in primitive and myeloid progenitor cells, whereas CD34+AC133- cells mainly consist of B cell and late erythroid progenitors. This corresponds to the highly reduced percentage of CD10+ B cells and the absence of CD71high erythroid progenitors on AC133+ selected BM cells. A portion of 0.2-0.7% of the AC133+ selected cells do not coexpress CD34. These cells are very small and define a uniform CD71-, CD117-, CD10-, CD38low, CD135+, HLA-DRhigh, CD45+ population with unknown delineation. Four color analysis on CD34+CD38- BM cells revealed that virtually all of these primitive cells express AC133. Using an improved liposome-enhanced labeling technique for the staining of weakly expressed antigens, subsets of this population could be identified which express the angiopoietin receptors TIE (67.6%) and TEK (36.8%), the vascular endothelial growth factor receptors FLT1 (7%), FLT4 (3.2%), and KDR (10.4%), or the receptor tyrosine kinases HER-2 (15.4%) and FLT3 (CD135; 77.6%). Our results suggest that the CD34+CD38- population is heterogeneous with respect to the expression of the analyzed receptor tyrosine kinases.
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PMID:Expression of novel surface antigens on early hematopoietic cells. 1037 8

The presence of contaminating tumor cells in autologous bone marrow or peripheral blood stem cell (PB-SC) preparations increase the likelihood of relapse in women receiving transplants for metastatic breast cancer. We describe a new technique for purging breast cancer cells (BCCs) that combines two independent strategies: (a) the specific enrichment of CD34+ progenitor stem cells by magnetic antibody cell separation (MACS), and then (b) infection of the contaminating BCCs with a recombinant adGAL-TEK marker/suicide gene adenovirus (ad-v), followed by the addition of ganciclovir (GCV). Infection with this ad-v results in three to four times greater expression of ad-v-delivered reporter gene in BCCs than in CD34+ cells. In addition -2 h, -low multiplicity of infection (50:1) adGAL-TEK infections of BCC lines (MCF-7 and BT474) eradicated >99% of BCCs after 72 h of exposure to 20 microM GCV. However, exposure to both adenovirus and GCV at the MOIs and doses used had little effect on hematopoietic stem cells to form colonies in colony-forming unit assays. adGAL-TEK infection in our model system (10(3)-10(5) BCCs added into 10(7) HSCs) also resulted in the 3 to 5 log eradication of clonogenic BCCs after the addition of GCV. MACS enrichment/purification of CD34+ cells from PB-SC contaminated with 2 x 10(6) to 5 x 10(7) BCCs followed by adGAL-TEK infection and GCV addition resulted in 5-7-log depletion of clonogenic BCCs as well as enrichment of CD34+ progenitor cells to >98%, with the recovery of >70% of hematopoietic stem cells. This adenoviral purging system is so robust that poor MACS purification, resulting in 1.5-log depletion of BCCs, still permits excellent ad-v infection and BCC killing.
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PMID:Purging of contaminating breast cancer cells from hematopoietic stem cell grafts by adenoviral GAL-TEK gene therapy and magnetic antibody cell separation. 1038 45

The TIE2 gene, also known as TEK, encodes a tyrosine kinase receptor that is required for the normal development of the vascular system during embryogenesis. TIE2 is specifically expressed in endothelial cells; however, the transcriptional mechanisms that regulate this highly restricted pattern of expression remain unknown. Here we demonstrate that a consensus octamer element located in the 5'-flanking region of TIE2 is required for normal expression in embryonic endothelial cells. Transgenic embryos carrying a TIE2/LacZ construct spanning 2.1 kilobases of upstream regulatory sequences exhibit expression of the reporter transgene specifically in endothelial cells. Site-directed mutagenesis of a consensus octamer element located in this region results in the loss of enhancer activity and significantly impairs the endothelial expression of the reporter transgene. Consistent with the in vivo data, in vitro DNA-protein binding studies show that the consensus octamer element displays an endothelial cell-specific pattern of binding, suggesting an interaction with a protein complex consisting of Oct1 and an endothelial cell-restricted cofactor. These data identify a novel role for the octamer element as an essential regulator of TIE2 expression, define the first known transcriptional pathway that mediates the expression of a developmental endothelial cell gene, and provide insights into the transcriptional mechanisms that regulate development of the vasculature during embryogenesis.
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PMID:Octamer-dependent in vivo expression of the endothelial cell-specific TIE2 gene. 1040 Jun 61

TEK (TIE2) and TIE (TIE1) are structurally related receptor tyrosine kinases expressed in endothelial cells and their precursors. Genetic studies in the mouse have revealed essential functions of both receptors in angiogenic expansion of the vasculature during development. As previously shown, mouse embryos homozygous for a disrupted Tek allele die by day 10.5 of embryogenesis due to endocardial defects, hemorrhaging, and impaired vascular network formation. Furthermore, TIE is required cell autonomously for endothelial cell survival and extension of the vascular network during late embryogenesis. Here we have investigated possible redundancy in the TEK and TIE signalling pathways during vascular development. Vasculogenesis proceeds normally in embryos lacking both TEK and TIE, although such embryos die early in gestation of multiple cardiovascular defects. Mosaic analysis revealed an absolute requirement for TEK in the endocardium at E10.5, whereas TEK and TIE are dispensable for the initial assembly of the rest of the vasculature. In contrast, both receptors are required in the microvasculature during late organogenesis and in essentially all blood vessels of the adult. This analysis demonstrates essential functions for TEK and TIE in maintaining the integrity of the mature vasculature.
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PMID:Interaction of the TEK and TIE receptor tyrosine kinases during cardiovascular development. 1049 91

Cutaneous malignant melanoma (CMM) is a common skin cancer. About 50% of CMM sporadic tumours have lost one copy of the chromosome 9p21 region. To identify genes involved in the initiation and/or progression of CMM we have characterised the 9p21 melanoma deleted region and screened the human expressed sequence tag (EST) databases (dbEST) to search for expressed genes. We have identified the gene that encodes the human orthologue of the rat phospholipase A2 activating protein (PLAP). PLAP was considered a potential candidate to be involved in malignant melanoma because it maps to the critical region for CMM and because the PLA2 gene has been identified as a modifier of the APC gene, responsible for the adenomatous polyposis phenotype in the mouse. PLAP encodes a protein of 738 amino acids and has a high DNA (90%) and protein (97%) sequence similarity with the rat and mouse PLAP protein. PLAP has a region of WD40 repeats in the amino-terminus, which allows us to include this protein in the superfamily of beta-transducin proteins. Northern blot hybridisation gave a fragment of 4.5 kb, with higher expression in heart compared to other tissues. PLAP was localised at chromosome 9p21, between marker AFM218xg11 and TEK. SSCP analysis of the coding region of PLAP revealed no variants in the studied samples, but one of six CMM samples analysed by RT-PCR showed specific inactivation of PLAP. Despite PLAP's important role in mediating several cellular responses and its localisation to the chromosome 9p21 region deleted in CMM, it is unlikely that point mutations or deletions in the coding region of PLAP are responsible for the initiation or progression of CMM. Further studies on PLAP inactivation should be performed to clarify its potential involvement in CMM.
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PMID:Cloning of the human phospholipase A2 activating protein (hPLAP) gene on the chromosome 9p21 melanoma deleted region. 1057 Oct 45

Vascular anomalies are congenital lesions that usually occur sporadically, but can be inherited. Previously, we have described that venous malformations, localized bluish-purple skin lesions, are caused by an activating mutation in the TIE2/TEK receptor. Moreover, we mapped another locus to chromosome 1p21-p22, for venous malformations with glomus cells (VM-GLOM). Here we report a physical map, based on 18 overlapping YAC clones, spanning this 5-Mb VMGLOM locus, from marker GATA63C06 to D1S2664. In addition, we report a sequence-ready PAC map of 46 clones covering 1.48 Mb within the YAC contig, a region to which we have restricted VMGLOM. We describe 21 new STSs and nine novel CA repeats, seven of which are polymorphic. These data will enable positional cloning of genes for diseases mapped to this locus, including the VMGLOM gene, likely a currently unknown regulator of vasculogenesis and/or angiogenesis.
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PMID:High-resolution physical and transcript map of the locus for venous malformations with glomus cells (VMGLOM) on chromosome 1p21-p22. 1094 76


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