Key Spec Table
|Species Reactivity||Key Applications||Host||Format||Antibody Type|
|H, M||IP, WB||Rb||Purified||Polyclonal Antibody|
|Presentation||0.1M Tris-glycine buffer, pH 7.4|
|Application||Anti-Abl SH3 Domain Antibody detects level of Abl SH3 Domain & has been published & validated for use in IP & WB.|
|Safety Information according to GHS|
|Storage and Shipping Information|
|Storage Conditions||1 year at -20°C|
|Material Size||250 µg|
|Anti- Abl SH3 domain (rabbit polyclonal IgG) - 2322035||2322035|
|Anti- Abl SH3 domain - DAM1725584||DAM1725584|
|Anti- Abl SH3 domain - DAM1770292||DAM1770292|
|Anti-Abl SH3 Domain - 0611045710||0611045710|
|Anti-Abl SH3 Domain - 14336||14336|
|Anti-Human Abl SH3 domain (rabbit polyclonal IgG) - DAM1460248||DAM1460248|
|Reference overview||Pub Med ID|
|Comparison of various kinds of bone marrow stem cells for the repair of infarcted myocardium: single clonally purified non-hematopoietic mesenchymal stem cells serve as a superior source.|
Shaoheng Zhang, Junbo Ge, Aijun Sun, Danling Xu, Juying Qian, Jinyi Lin, Yan Zhao, Haifeng Hu, Ying Li, Keqiang Wang, Yunzeng Zou
Journal of cellular biochemistry 99 1132-47 2006
A variety of adult stem cells have been used to transplant into the infarcted (MI) heart, however, comparative studies are lacking to show more suitable source of cells for transplantation. We have identified a single non-hematopoietic mesenchymal stem cell subpopulation (snMSCs) isolated from human bone marrow and clonally purified, that over 99% of them expressed MSC marker proteins and cardiomyocyte marker proteins when induction in vitro. We also compared the effects of the snMSCs with unpurified MSC (uMSCs), mononuclear cells (BMMNCs), or peripheral blood mononuclear cells (PBMNCs) on myocardial repair after induction of MI in rats. Ninety days later, we observed a better cardiac function assessed by ejection fraction, fraction of shortening and lung wet/dry weight ratios, less remodeling of left ventricle (LV), lower collagen density in the LV, and more vessels in the ischemic wall in the snMSCs transplantation group than in other cell-transplanted groups. Furthermore, the transplanted cells expressing cardiomyocyte specific proteins or vascular endothelial cell marker proteins were more in the snMSCs group than in other ones. We conclude that transplantation with single clonally purified MSCs seems to be more beneficial to the cardiac repair than with other stem cells after MI.
|Bcr-Abl resistance screening predicts a limited spectrum of point mutations to be associated with clinical resistance to the Abl kinase inhibitor nilotinib (AMN107).|
von Bubnoff, N; Manley, PW; Mestan, J; Sanger, J; Peschel, C; Duyster, J
Blood 108 1328-33 2006
In advanced-phase chronic myeloid leukemia (CML), resistance to imatinib mesylate is associated with point mutations in the BCR-ABL kinase domain. A new generation of potent ABL kinase inhibitors is undergoing clinical evaluation. It is important to generate specific resistance profiles for each of these compounds, which could translate into combinatorial and sequential treatment strategies. Having characterized nilotinib (AMN107) against a large panel of imatinib mesylate-resistant Bcr-Abl mutants, we investigated which mutants might arise under nilotinib therapy using a cell-based resistance screen. In contrast to imatinib mesylate, resistance to nilotinib was associated with a limited spectrum of Bcr-Abl kinase mutations. Among these were mutations affecting the P-loop and T315I. Rarely emerging resistant colonies at a concentration of 400 nM nilotinib exclusively expressed the T315I mutation. With the exception of T315I, all of the mutations that were identified were effectively suppressed when the nilotinib concentration was increased to 2000 nM, which falls within the peak-trough range in plasma levels (3.6-1.7 microM) measured in patients treated with 400 mg twice daily. Our findings suggest that nilotinib might be superior to imatinib mesylate in terms of the development of resistance. However, our study indicates that clinical resistance to nilotinib may be associated with the predominant emergence of T315I.
|Calpain regulation of cytoskeletal signaling complexes in von Willebrand factor-stimulated platelets. Distinct roles for glycoprotein Ib-V-IX and glycoprotein IIb-IIIa (integrin alphaIIbbeta3) in von Willebrand factor-induced signal transduction.|
Y Yuan,S M Dopheide,C Ivanidis,H H Salem,S P Jackson
The Journal of biological chemistry 272 1997
The adhesion of platelets to sites of vascular injury is critically dependent on the binding of subendothelial bound von Willebrand factor (vWf) to the platelet surface glycoprotein complexes, GP Ib-V-IX and GP IIb-IIIa (integrin alphaIIbbeta3). There is growing evidence that the binding of vWf to these receptors is not only essential for stable platelet adhesion but is also important for the transduction of activation signals required for changes in platelet morphology, granule secretion, and platelet aggregation. In this study we have investigated signaling events induced by vWf binding to GP Ib-V-IX in both spreading and aggregated platelets. The adhesion of platelets to vWf resulted in dramatic actin filament reorganization, as assessed by immunofluorescence with fluorescein isothiocyanate-conjugated phalloidin, and the cytoskeletal recruitment of various structural proteins (talin and integrin alphaIIbbeta3) and signaling enzymes (pp60c-src, focal adhesion kinase (FAK), phosphatidylinositol 3-kinase (PI 3-kinase), and protein-tyrosine phosphatase (PTP)-1B). Time course experiments in both spreading and aggregated platelets revealed that talin, FAK, and PTP-1B were proteolyzed after translocation to the cytoskeleton. The proteolysis of these proteins was dependent on the presence of extracellular calcium and was specifically inhibited by pretreating platelets with the membrane-permeable calpain inhibitors calpeptin, E64d, and MDL 28,170, but not with the membrane-impermeable inhibitors leupeptin, E64, and calpastatin. The cytoskeletal translocation of signaling enzymes in vWf-stimulated platelets was abolished by pretreating platelets with an anti-GP Ib-V-IX antibody but was unaffected by blocking ligand binding to integrin alphaIIbbeta3. In contrast, calpain activation in vWf-stimulated platelets required ligand binding to both GP Ib-V-IX and integrin alphaIIbbeta3. The activation of calpain in both spreading and aggregated platelets resulted in a substantial decrease in the level of tyrosine phosphorylation of multiple platelet proteins and was associated with a 50-80% reduction in the amount of cytoskeletal associated talin, integrin alphaIIbbeta3, PI 3-kinase, FAK, pp60(c-)src, and PTP-1B. These studies suggest a potentially important role for calpain in regulating the formation and/or stability of cytoskeletal signaling complexes in vWf-stimulated platelets. Furthermore, they demonstrate distinct roles for GP Ib-V-IX and integrin alphaIIbbeta3 in vWf-induced signal transduction.
|Abl tyrosine protein kinase.|
Semin. Immunol., 7: 255-66 (1995) 1995
Mammalian c-Abl belongs to an evolutionary conserved family of non-receptor tyrosine kinases. It is distributed both in the cytoplasm in association with F-actin, and in the nucleus where it binds chromatin. The normal function of c-Abl is poorly understood. Nevertheless, there has been rapid progress in the characterization of the structural features, signal transduction pathways, substrates and ligands involved in the action of c-Abl and Abl-derived oncogenes. These developments suggest that several mechanisms co-operate to allow regulation of normal cell growth by c-Abl and induction of leukemias by Bcr-abl.
|Abl-mediated transformation, immunoglobulin gene rearrangements and arrest of B lymphocyte differentiation.|
Semin. Cancer Biol., 5: 95-102 (1994) 1994
The abl oncogene was originally discovered in Abelson virus, a murine retrovirus. This virus and the protein tyrosine kinase encoded by abl are well known for their ability to transform B lymphocyte progenitors. Most of the transformed cells resemble a normal B lineage progenitor called a pre-B cell and appear to be arrested in differentiation at the stage of immunoglobulin light chain gene rearrangement. Recent evidence obtained using temperature-sensitive Abelson virus mutants provides direct support for this idea. Lymphoid cells transformed by one such virus undergo light chain rearrangement soon after shift to the nonpermissive temperature. This event is accompanied by several changes classically associated with light chain gene rearrangement including increased activity of the NF-kappa B transcription factor, expression of light chain RNAs and increased levels of expression of the RAG-1 and RAG-2 genes. Although the mechanism by which abl protein blocks the activity of these factors is not yet known, these data suggest that tyrosine phosphorylation may be intimately connected to regulation of early B cell development and expression of genes that are central to all phases of antigen receptor gene rearrangement.
|T-cell immunity to oncogenic proteins including mutated ras and chimeric bcr-abl.|
Cheever, M A, et al.
Ann. N. Y. Acad. Sci., 690: 101-12 (1993) 1993
The process of malignant transformation can be ascribed to a series of characteristics and definable mutations of genes which encode proteins that control cell growth and differentiation. During the course of malignant transformation the cancer-related genes are altered by a variety of mechanisms including translocations, deletions, and point mutations which commonly result in the expression of aberrant proteins. Our laboratory has focused on determining the extent to which cancer-specific proteins expressed by aberrant cancer-related genes can function as tumor-specific antigens. The current paper reviews our studies with two prototype cancer-specific proteins, mutated p21ras protein and chimeric p210bcr-abl protein. Ras protooncogenes are activated by point mutation in approximately 20% of human malignancies. The mutations occur primarily at codons 12 or 61 and result in the expression of p21ras proteins with single substituted amino acids. Only a limited number of amino acid substitutions occur. Murine studies demonstrate that immunization with synthetic peptides corresponding to the mutated segment can elicit both class II restricted CD4+ helper/inducer T-cell responses and class I restricted CD8+ cytotoxic T-cell responses specific for mutated p21ras protein. In addition, the existence in vivo of tumors expressing mutated ras proteins can be detected by assaying for T-cell immunity to the mutated segment of ras protein. Preliminary human studies show that some patients with colon cancer have existent antibody responses to p21ras protein, implying the possible existence of autochthonous T-cell immunity to mutated ras proteins in those patients. In chronic myelogenous leukemia the human c-abl protooncogene from chromosome 9 is translocated to the specific breakpoint cluster (bcr) region on chromosome 22. The translocation results in the formation of a bcr-abl fusion gene that encodes at 210-kD chimeric protein. The joining region segment of chimeric bcr-abl protein is composed of a unique combination of c-abl and bcr amino acids and is expressed only by malignant cells. Studies demonstrate that immunization of mice with synthetic peptides corresponding to the joining region segment can elicit class II restricted CD4+ T-cell responses to p210bcr-abl proteins. Preliminary studies show that bcr-abl peptides can bind in the groove of both murine and human class I MHC molecules and can elicit bcr-abl peptide-specific cytotoxic T lymphocytes (CTL). Whether bcr-abl peptide-specific CTL can lyse cells expressing bcr-abl protein is a yet unknown. In summary, the results of the studies reviewed confirm that cancer-specific oncogenic proteins can serve as tumor-specific antigens.
|Abl tyrosine kinase in signal transduction and cell-cycle regulation.|
Wang, J Y
Curr. Opin. Genet. Dev., 3: 35-43 (1993) 1993
Although the biological function of the c-Abl tyrosine kinase remains unsolved, potentially productive avenues towards the elucidation of that function have been identified by recent progress. An F-actin binding and a sequence-specific DNA-binding domain have been discovered in c-Abl, and DNA binding has been shown to be cell-cycle regulated. Deletion of those two domains in the mouse c-Abl results in a loss of biological function despite the production of an active tyrosine kinase. These findings suggest a role for c-Abl in the regulation of processes occurring on F-actin and on specific DNA elements.
|Induction of mouse thymocyte apoptosis by inhibitors of tyrosine kinases is associated with dephosphorylation of nuclear proteins.|
Y Azuma,Y Onishi,Y Sato,H Kizaki
Cellular immunology 152 1993
Incubation of mouse thymocytes with the protein tyrosine kinase inhibitors herbimycin A and methyl-2,5-dihydroxycinnamate induced a decreased and altered profile of nuclear phosphotyrosine proteins in parallel with an increase in internucleosomal DNA fragmentation and cell death dose-dependently. No change in the profile of cytoplasmic phosphotyrosine proteins was observed. DNA fragmentation was dependent on the synthesis of RNA and protein, suggesting that the inhibition of tyrosine phosphorylation of the nuclear proteins induces apoptosis. DNA fragmentation was enhanced by simultaneous incubation with phorbol esters capable of activating protein kinase C. Genistein, another inhibitor of protein tyrosine kinase, induced DNA fragmentation more rapidly than herbimycin A, but there was no predominant alteration of phosphotyrosine proteins in early incubation, suggesting that genistein may induce apoptosis by a mechanism other than direct inhibition of protein tyrosinekinase activity.