Key Spec Table
|Species Reactivity||Key Applications||Host||Format||Antibody Type|
|H||FC, IP, WB, IHC, IH(P)||M||Purified||Monoclonal Antibody|
|Description||Anti-Integrin β3 Antibody, clone PM6/13|
|Safety Information according to GHS|
|Storage and Shipping Information|
|Storage Conditions||For use within 1 month of purchase store at +4°C, for long term storage aliquot antibody into small volumes and store at -20°C.|
|Material Size||100 µg|
|MOUSE ANTI-HUMAN CD61||2487697|
|MOUSE ANTI-HUMAN CD61 MONOCLONAL ANTIBODY - 2427483||2427483|
|MOUSE ANTI-HUMAN CD61 - 2154070||2154070|
|MOUSE ANTI-HUMAN CD61 - 2952658||2952658|
|MOUSE ANTI-HUMAN CD61 MONOCLONAL ANTIBODY - 2106896||2106896|
|MOUSE ANTI-HUMAN CD61 MONOCLONAL ANTIBODY - 2327720||2327720|
|Reference overview||Species||Pub Med ID|
|A novel family of RGD-containing disintegrins (Tablysin-15) from the salivary gland of the horsefly Tabanus yao targets αIIbβ3 or αVβ3 and inhibits platelet aggregation and angiogenesis.|
Ma, D; Xu, X; An, S; Liu, H; Yang, X; Andersen, JF; Wang, Y; Tokumasu, F; Ribeiro, JM; Francischetti, IM; Lai, R
Thrombosis and haemostasis 105 1032-45 2011
A novel family of RGD-containing molecules (Tablysin-15) has been molecularly characterised from the salivary gland of the haematophagous horsefly Tabanus yao. Tablysin-15 does not share primary sequence homology to any disintegrin discovered so far, and displays an RGD motif in the N-terminus of the molecule. It is also distinct from disintegrins from Viperidae since its mature form is not released from a metalloproteinase precursor. Tablysin-15 exhibits high affinity binding for platelet αIIbβ3 and endothelial cell αVβ3 integrins, but not for α5β1 or α2β1. Accordingly, it blocks endothelial cell adhesion to vitronectin (IC50 ~1 nM) and marginally to fibronectin (IC50 ~1 μM), but not to collagen. It also inhibits fibroblast growth factor (FGF)-induced endothelial cell proliferation, and attenuates tube formation in vitro. In platelets, Tablysin-15 inhibits aggregation induced by collagen, ADP and convulxin, and prevents static platelet adhesion to immobilised fibrinogen. In addition, solid-phase assays and flow cytometry demonstrates that αIIbβ3 binds to Tablysin-15. Moreover, immobilised Tablysin-15 supports platelet adhesion by a mechanism which was blocked by anti-integrin αIIbβ3 monoclonal antibody (e.g. abciximab) or by EDTA. Furthermore, Tablysin-15 dose-dependently attenuates thrombus formation to collagen under flow. Consistent with these findings, Tablysin-15 displays antithrombotic properties in vivo suggesting that it is a useful tool to block αIIbβ3, or as a prototype to develop antithrombotics. The RGD motif in the unique sequence of Tablysin-15 represents a novel template for studying the structure-function relationship of the disintegrin family of inhibitors.
|Role of the beta-subunit arginine/lysine finger in integrin heterodimer formation and function.|
Vineet Gupta,José Luis Alonso,Takashi Sugimori,Makram Essafi,Makram Issafi,Jiang-Ping Xiong,M Amin Arnaout
Journal of immunology (Baltimore, Md. : 1950) 180 2008
Formation of the integrin alphabeta heterodimer is essential for cell surface expression and function. At the core of the alphabeta interface is a conserved Arg/Lys finger from the beta-subunit that inserts into a cup-like cage formed of two layers of aromatic residues in the alpha-subunit. We evaluated the role of this residue in heterodimer formation in an alphaA-lacking and an alphaA-containing integrin alphaVbeta3 and alphaMbeta2 (CD11b/CD18), respectively. Arg261 of beta3 was mutated to Ala or Glu; the corresponding Lys252 of beta2 was mutated to Ala, Arg, Glu, Asp, or Phe; and the effects on heterodimer formation in each integrin examined by ELISA and immunoprecipitation in HEK 293 cells cotransfected with plasmids encoding the alpha- and beta-subunits. The Arg261Glu (but not Arg261Ala) substitution significantly impaired cell surface expression and heterodimer formation of alphaVbeta3. Although Lys252Arg, and to a lesser extent Lys252Ala, were well tolerated, each of the remaining substitutions markedly reduced cell surface expression and heterodimer formation of CD11b/CD18. Lys252Arg and Lys252Ala integrin heterodimers displayed a significant increase in binding to the physiologic ligand iC3b. These data demonstrate an important role of the Arg/Lys finger in formation of a stable integrin heterodimer, and suggest that subtle changes at this residue affect the activation state of the integrin.Full Text Article
|Pharmacology of the novel antiangiogenic peptide ATN-161 (Ac-PHSCN-NH2): observation of a U-shaped dose-response curve in several preclinical models of angiogenesis and tumor growth.|
Doñate, F; Parry, GC; Shaked, Y; Hensley, H; Guan, X; Beck, I; Tel-Tsur, Z; Plunkett, ML; Manuia, M; Shaw, DE; Kerbel, RS; Mazar, AP
Clinical cancer research : an official journal of the American Association for Cancer Research 14 2137-44 2008
ATN-161 (Ac-PHSCN-NH(2)) is an integrin-binding peptide that is currently in phase II trials in cancer patients. This peptide has been shown to have antitumor activity in a number of different preclinical models.In this study, we examined the binding, biodistribution, and dose and biomarker response of ATN-161 in several animal models.ATN-161 bound to the beta subunit of a number of different integrins implicated in tumor growth and progression, which depended on its cysteine thiol. The peptide had antiangiogenic activity in the Matrigel plug model, and this activity could be reversed by inhibitors of protein kinase A, an effector of alpha(5)beta(1)-dependent angiogenesis. A labeled analogue of ATN-161, ATN-453, localized to neovessels but not to preexisting vasculature in vivo. The half-life of the peptide when localized to a tumor was much longer than in plasma. Dose-response studies in the Matrigel plug model of angiogenesis or a Lewis lung carcinoma model of tumor growth showed a U-shaped dose-response curve with 1 to 10 mg/kg given thrice a week, being the optimal dose range of ATN-161. Two additional pharmacodynamic models of angiogenesis (dynamic contrast-enhanced magnetic resonance imaging and measurement of endothelial cell progenitors) also revealed U-shaped dose-response curves.The presence of a U-shaped dose-response curve presents a significant challenge to identifying a biologically active dose of ATN-161. However, the identification of biomarkers of angiogenesis that also exhibit this same U-shaped response should allow the translation of those biomarkers to the clinic, allowing them to be used to identify the active dose of ATN-161 in phase II studies.
|FAK-independent alphavbeta3 integrin-EGFR complexes rescue from anoikis matrix-defective fibroblasts.|
Zoppi, Nicoletta, et al.
Biochim. Biophys. Acta, 1783: 1177-88 (2008) 2008
|Loss of dipeptidyl peptidase IV immunostaining discriminates malignant melanomas from deep penetrating nevi.|
Roesch, A; Wittschier, S; Becker, B; Landthaler, M; Vogt, T
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 19 1378-85 2006
The deep penetrating nevus is a rare variant of benign melanocytic nevus with histologic features mimicking vertical growth phase, nodular malignant melanoma. In this study, we expand on the search for new complementary discriminating markers by analyzing a selection of both cell cycle-related factors, such as retinoblastoma protein and phospho-retinoblastoma protein Ser795 as indicators for retinoblastoma protein activation/inactivation status, and invasion-related factors, such as matrix metalloproteinase-1, matrix metalloproteinase-2, membrane-type matrix metalloproteinase-1 and integrin beta3. MIB-1/Ki-67 was analyzed as an example for a common proliferation marker. Dipeptidyl peptidase IV/CD26 was analyzed as a marker affecting both proliferation and invasion of malignant melanocytic tumors. Semiquantitative assessment of both immunolocalization and immunoreactivity of retinoblastoma protein and phospho-retinoblastoma protein Ser795, MIB-1/Ki-67, matrix metalloproteinase-1, matrix metalloproteinase-2, membrane-type matrix metalloproteinase-1 and integrin beta3 revealed no consistent differences between deep penetrating nevi (n=14) and matched cases of nodular malignant melanomas (n=10). Matrix metalloproteinase-1 and matrix metalloproteinase-2 immunostaining of some deep penetrating nevi even exceeded that of nodular malignant melanomas. Membrane-type matrix metalloproteinase-1 expression scores of nodular malignant melanomas were higher than those of deep penetrating nevi, which was, however, not significantly discriminative. In contrast, immunostaining of dipeptidyl peptidase IV was significantly discriminative due to a consistent lack of dipeptidyl peptidase IV-expression in nodular malignant melanomas. These results add evidence that among the selected markers supposed to be relevant for melanoma progression the presence of dipeptidyl peptidase IV can be used to support diagnosis of deep penetrating nevi in doubtful cases. As loss of dipeptidyl peptidase IV may also be causally linked to the transition of invasive to metastatic phenotypes, the molecular mechanisms downstream of dipeptidyl peptidase IV deserve to be studied in more detail in future investigations.
|On the mechanism of thrombin-induced angiogenesis: involvement of alphavbeta3-integrin.|
Tsopanoglou, Nikos E, et al.
Am. J. Physiol., Cell Physiol., 283: C1501-10 (2002) 2002
Thrombin has been reported to be a potent angiogenic factor both in vitro and in vivo, and many of the cellular effects of thrombin may contribute to activation of angiogenesis. In this report we show that thrombin-treatment of human endothelial cells increases mRNA and protein levels of alphavbeta3-integrin. This thrombin-mediated effect is specific, dose dependent, and requires the catalytic site of thrombin. In addition, thrombin interacts with alphavbeta3 as demonstrated by direct binding of alphavbeta3 protein to immobilized thrombin. This interaction of thrombin with alphavbeta3-integrin, which is an angiogenic marker in vascular tissue, is of functional significance. Immobilized thrombin promotes endothelial cells attachment, migration, and survival. Antibody to alphavbeta3 or a specific peptide antagonist to alphavbeta3 can abolish all these alphavbeta3-mediated effects. Furthermore, in the chick chorioallantoic membrane system, the antagonist peptide to alphavbeta3 diminishes both basal and the thrombin-induced angiogenesis. These results support the pivotal role of thrombin in activation of endothelial cells and angiogenesis and may be related to the clinical observation of neovascularization within thrombi.
|Anti-Integrin beta3, clone PM6/13 - Data Sheet|