Key Spec Table
|Species Reactivity||Key Applications||Host||Format||Antibody Type|
|H, M||IP, NEUT||M||Purified||Monoclonal Antibody|
|Presentation||Purified mouse monoclonal IgG1 in buffer containing 10 mM PBS, pH 7.4. Frozen solution.|
|Safety Information according to GHS|
|Material Size||100 µg|
|Reference overview||Pub Med ID|
|Nuclear actin filaments recruit cofilin and actin-related protein 3, and their formation is connected with a mitotic block.|
Kalendová, A; Kalasová, I; Yamazaki, S; Uličná, L; Harata, M; Hozák, P
Histochemistry and cell biology 142 139-52 2014
Although actin monomers polymerize into filaments in the cytoplasm, the form of actin in the nucleus remains elusive. We searched for the form and function of β-actin fused to nuclear localization signal and to enhanced yellow fluorescent protein (EN-actin). Our results reveal that EN-actin is either dispersed in the nucleoplasm (homogenous EN-actin) or forms bundled filaments in the nucleus (EN-actin filaments). Formation of such filaments was not connected with increased EN-actin levels. Among numerous actin-binding proteins tested, only cofilin is recruited to the EN-actin filaments. Overexpression of EN-actin causes increase in the nuclear levels of actin-related protein 3 (Arp3). Although Arp3, a member of actin nucleation complex Arp2/3, is responsible for EN-actin filament nucleation and bundling, the way cofilin affects nuclear EN-actin filaments dynamics is not clear. While cells with homogenous EN-actin maintained unaffected mitosis during which EN-actin re-localizes to the plasma membrane, generation of nuclear EN-actin filaments severely decreases cell proliferation and interferes with mitotic progress. The introduction of EN-actin manifests in two mitotic-inborn defects-formation of binucleic cells and generation of micronuclei-suggesting that cells suffer aberrant cytokinesis and/or impaired chromosomal segregation. In interphase, nuclear EN-actin filaments passed through chromatin region, but do not co-localize with either chromatin remodeling complexes or RNA polymerases I and II. Surprisingly presence of EN-actin filaments was connected with increase in the overall transcription levels in the S-phase by yet unknown mechanism. Taken together, EN-actin can form filaments in the nucleus which affect important cellular processes such as transcription and mitosis.
|Inhibition of doxorubicin-induced HER3-PI3K-AKT signalling enhances apoptosis of ovarian cancer cells.|
Martin Bezler,Jan G Hengstler,Axel Ullrich
Molecular oncology 6 2012
Resistance to chemotherapy is a serious problem for the successful treatment of ovarian cancer patients but signalling pathways that contribute to this chemoinsensitivity are largely unknown. We demonstrate that the chemotherapeutic drug doxorubicin induces activation of the HER3-PI3K-AKT signalling cascade in ovarian cancer cells. We further show that the induction of this anti-apoptotic signalling pathway is based on upregulated expression of HER3 ligands, their shedding by the metalloprotease ADAM17, and is dependent on the HER2 receptor. The doxorubicin-mediated activation of this important survival cascade can be blocked by the kinase inhibitors lapatinib or erlotinib as well as by the therapeutic monoclonal antibody trastuzumab. Inhibition of the doxorubicin-induced activation of HER3-PI3K-AKT signalling significantly increased apoptosis of ovarian cancer cells. Besides doxorubicin, treatment of cells with cisplatin resulted in activation of the HER3 receptor whereas other chemotherapeutics did not show this effect. The increase in HER3 phosphorylation was detected in well-established ovarian cancer cell lines which originate from patients previously treated with these chemotherapeutic drugs. Based on these results, we postulate that activation of the HER3-PI3K-AKT cascade represents a major mechanism of chemoresistance in ovarian cancer.
|Ionizing radiation stimulates existing signal transduction pathways involving the activation of epidermal growth factor receptor and ERBB-3, and changes of intracellular calcium in A431 human squamous carcinoma cells.|
D G Todd, R B Mikkelsen, W K Rorrer, K Valerie, R K Schmidt-Ullrich
Journal of receptor and signal transduction research 19 885-908 1999
Previous studies demonstrated that ionizing radiation activates the epidermal growth factor receptor (EGFR), as measured by Tyr autophosphorylation, and induces transient increases in cytosolic free [Ca2+], [Ca2+]f. The mechanistic linkage between these events has been investigated in A431 squamous carcinoma cells with the EGFR Tyr kinase inhibitor, AG1478. EGFR autophosphorylation induced by radiation at doses of 0.5-5 Gy or EGF concentrations of 1-10 ng/ml is inhibited by >75% at 100 nM AG1478. Activation of EGFR enhances IP3 production as a result of phospholipase C (PLC) activation. At the doses used, radiation stimulates Tyr phosphorylation of both, PLCgamma and erbB-3, and also mediates the association between erbB-3 and PLCgamma not previously described. The increased erbB-3 Tyr phosphorylation is to a significant extent due to transactivation by EGFR as >70% of radiation- and EGF-induced erbB-3 Tyr phosphorylation is inhibited by AG 1478. The radiation-induced changes in [Ca2+]f are dependent upon EGFR, erbB-3 and PLCgamma activation since radiation stimulated IP3 formation and Ca2+ oscillations are inhibited by AG1478, the PLCgamma inhibitor U73122 or neutralizing antibody against an extracellular epitope of erbB-3. These results demonstrate that radiation induces qualitatively and quantitatively similar responses to EGF in stimulation of the plasma membrane-associated receptor Tyr kinases and immediate downstream effectors, such as PLCgamma and Ca2+.
|An immunological approach reveals biological differences between the two NDF/heregulin receptors, ErbB-3 and ErbB-4.|
Chen, X, et al.
J. Biol. Chem., 271: 7620-9 (1996) 1996
|C-erbB-3 in human breast carcinoma: expression and relation to prognosis and established prognostic indicators|
Travis, A, et al
Br J Cancer, 74:229-33 (1996) 1996
|Isolation and characterization of ERBB3, a third member of the ERBB/epidermal growth factor receptor family: evidence for overexpression in a subset of human mammary tumors|
Kraus, M H, et al
Proc Natl Acad Sci USA, 86:9193-7 (1989) 1989