Pd–Cu-Catalyzed Synthesis of Alk-5-en-7-yn-2-ones

2018 ◽  
Vol 88 (10) ◽  
pp. 2197-2199
Author(s):  
R. N. Shakhmaev ◽  
A. Sh. Sunagatullina ◽  
E. A. Abdullina ◽  
V. V. Zorin
Keyword(s):  
Alk 5

Differential expression of transforming growth factor-beta receptors in rat kidney development

1997 ◽  
Vol 273 (3) ◽  
pp. F386-F395 ◽  
Author(s):  
M. E. Choi ◽  
A. Liu ◽  
B. J. Ballermann
Keyword(s):  
Transforming Growth Factor Beta ◽  
Kidney Development ◽  
Transforming Growth Factor ◽  
Rat Kidney ◽  
Neonatal Rat ◽  
Tgf Beta ◽  
Adult Rat ◽  
Beta Receptors ◽  
Growth Factor Beta ◽  
Alk 5

Transforming growth factor-beta 1 (TGF-beta 1) is strongly expressed during embryogenesis and in sites undergoing intense development and morphogenesis. Two receptor serine/threonine kinases (types I and II) have been identified as signal-transducing TGF-beta receptors. This study was undertaken to further explore the role of the distinct TGF-beta receptors during kidney development. The species-specific sequence information for the two T beta R-I, namely, activin receptor-like kinase-5 (ALK-5) and Tsk7L, in the rat was sought. Two full-length T beta R-I cDNAs were cloned from a neonatal rat kidney and lung libraries, and sequencing revealed that they were the rat homologs of human ALK-5 and murine Tsk7L. Both types I and II TGF-beta receptors are expressed in the kidney as determined by Northern blot analysis. T beta R-II mRNA abundance was significantly greater in the neonatal rat kidney compared with the adult rat kidney. Similarly, ALK-5 mRNA was more highly expressed in the fetal and neonatal rat kidney than the adult rat kidney. In contrast, there was no significant difference in Tsk7L mRNA abundance among the fetal, neonatal, and adult rat kidney. Thus, based on these findings, both T beta R-II and ALK-5 are developmentally regulated in the kidney. Increased expression of T beta R-II and ALK-5 proteins in the developing kidney was confirmed by immunohistochemistry. Interestingly, the two TGF-beta receptors did not entirely colocalize, raising the intriguing possibility that other TGF-beta signaling receptors may be involved.

Serelaxin inhibits differentiation and fibrotic behaviors of cardiac fibroblasts by suppressing ALK-5/Smad2/3 signaling pathway

2018 ◽  
Vol 362 (1) ◽  
pp. 17-27 ◽  
Author(s):  
Xue-ping Wu ◽  
Hai-jie Wang ◽  
Yong-li Wang ◽  
Hao-ran Shen ◽  
Yu-zhen Tan
Keyword(s):  
Signaling Pathway ◽  
Cardiac Fibroblasts ◽  
Alk 5

Palladium-Catalyzed [3 + 2] Intramolecular Cycloaddition of Alk-5-enylidenecyclopropanes

2006 ◽  
Vol 128 (2) ◽  
pp. 384-385 ◽  
Author(s):  
Moisés Gulías ◽  
Rebeca García ◽  
Alejandro Delgado ◽  
Luis Castedo ◽  
José L. Mascareñas
Keyword(s):  
Intramolecular Cycloaddition ◽  
Palladium Catalyzed ◽  
Alk 5

scholarly journals Modulation of TGF-β signaling by endoglin in murine hemangioblast development and primitive hematopoiesis

Blood ◽  
2011 ◽  
Vol 118 (1) ◽  
pp. 88-97 ◽  
Author(s):  
Liying Zhang ◽  
Alessandro Magli ◽  
Jacquelyn Catanese ◽  
Zhaohui Xu ◽  
Michael Kyba ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Es Cells ◽  
Transforming Growth Factor Β ◽  
Early Developmental Stage ◽  
Type I ◽  
Hematopoietic Development ◽  
Downstream Target ◽  
Primitive Hematopoiesis ◽  
Alk 5

Abstract Endoglin (Eng), an accessory receptor for the transforming growth factor β (TGF-β) superfamily, is required for proper hemangioblast and primitive hematopoietic development. However the mechanism by which endoglin functions at this early developmental stage is currently unknown. Transcriptional analyses of differentiating eng−/− and eng+/+ ES cells revealed that lack of endoglin leads to profound reductions in the levels of key hematopoietic regulators, including Scl, Lmo2, and Gata2. We also detected lower levels of phosphorylated Smad1 (pSmad1), a downstream target signaling molecule associated with the TGF-β pathway. Using doxycycline-inducible ES cell lines, we interrogated the TGF-β signaling pathway by expressing activated forms of ALK-1 and ALK-5, type I receptors for TGF-β. Our results indicate that ALK-1 signaling promotes hemangioblast development and hematopoiesis, as evidenced by colony assays, gene expression and FACS analyses, whereas signaling by ALK-5 leads to the opposite effect, inhibition of hemangioblast and hematopoietic development. In Eng−/− ES cells, ALK-1 rescued both the defective hemangioblast development, and primitive erythropoiesis, indicating that ALK-1 signaling can compensate for the absence of endoglin. We propose that endoglin regulates primitive hematopoiesis by modulating the activity of the Smad1/5 signaling pathway in early stages of development.

TGF-(beta) type I receptor/ALK-5 and Smad proteins mediate epithelial to mesenchymal transdifferentiation in NMuMG breast epithelial cells

1999 ◽  
Vol 112 (24) ◽  
pp. 4557-4568 ◽  
Author(s):  
E. Piek ◽  
A. Moustakas ◽  
A. Kurisaki ◽  
C.H. Heldin ◽  
P. ten Dijke
Keyword(s):  
Transforming Growth Factor ◽  
Activin A ◽  
Nuclear Accumulation ◽  
Type I ◽  
Beta Catenin ◽  
Tgf Beta ◽  
Mesenchymal Transition ◽  
Smad Proteins ◽  
Mesenchymal Transformation ◽  
Alk 5

The capacities of different transforming growth factor-(beta) (TGF-(beta)) superfamily members to drive epithelial to mesenchymal transdifferentiation of the murine mammary epithelial cell line NMuMG were investigated. TGF-(beta)1, but not activin A or osteogenic protein-1 (OP-1)/bone morphogenetic protein-7 (BMP-7), was able to induce morphological transformation of NMuMG cells as shown by reorganisation of the actin cytoskeleton and relocalisation/downregulation of E-cadherin and (beta)-catenin, an effect that was abrogated by the more general serine/threonine kinase and protein kinase C inhibitor, staurosporine. TGF-(beta)1 bound to TGF-(beta) type I receptor (T(beta)R-I)/ALK-5 and T(beta)R-II, but not to activin type I receptor (ActR-I)/ALK-2. Activin A bound to ActR-IB/ALK-4 and ActR-II, and BMP-7 bound to ActR-I/ALK-2, BMP type I receptor (BMPR-I)/ALK-3, ActR-II and BMPR-II. TGF-(beta)1 and BMP-7 activated the Smad-binding element (SBE)(4) promoter with equal potency, whereas activin A had no effect. Transfection of constitutively active (CA)-ALK-4 activated the 3TP promoter to the same extent as TGF-(beta)1 and CA-ALK-5 indicating that activin signalling downstream of type I receptors was functional in NMuMG cells. In agreement with this, activin A induced low levels of plasminogen activator inhibitor I expression compared to the high induction by TGF-(beta)1. In contrast to activin A and BMP-7, TGF-(beta)1 strongly induced Smad2 phosphorylation. Consistent with these findings, TGF-(beta)1 induced the nuclear accumulation of Smad2 and/or Smad3. In addition, NMuMG cells transiently infected with adenoviral vectors expressing high level CA-ALK-5 exhibited full transdifferentiation. On the other hand, infections with low level CA-ALK-5, which alone did not result in transdifferentiation, together with Smad2 and Smad4, or with Smad3 and Smad4 led to transdifferentiation. In conclusion, TGF-(beta)1 signals potently and passes the activation threshold to evoke NMuMG cell transdifferentiation. The TGF-(beta) type I receptor (ALK-5) and its effector Smad proteins mediate the epithelial to mesenchymal transition. Activin A does not induce mesenchymal transformation, presumably because the number of activin receptors is limited, while BMP-7-initiated signalling cannot mediate transdifferentiation.

scholarly journals The role of Alk-1 and Alk-5 in the mechanosensing of chondrocytes

2014 ◽  
Vol 19 (4) ◽  
Author(s):  
Patricia Sanz-Ramos ◽  
Javier Dotor ◽  
Iñigo Izal-Azcárate
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Peptide Inhibitors ◽  
Mechanical Environment ◽  
Chondrocyte Phenotype ◽  
Cartilage Cells ◽  
Alk 5

AbstractWe aim to demonstrate the role of Alk receptors in the response of hydrogel expansion. Chondrocytes from rat knees were cultured onto plastic and hydrogel surfaces. Alk-1 and Alk-5 were overexpressed or silenced and the effects on cells during expansion were tested and confirmed using peptide inhibitors for TGFβ. Overexpression of Alk-5 and silencing of Alk-1 led to a loss of the chondrocyte phenotype, proving that they are key regulators of chondrocyte mechanosensing. An analysis of the gene expression profile during the expansion of these modified cartilage cells in plastic showed a better maintenance of the chondrocyte phenotype, at least during the first passages. These passages were also assayed in a mouse model of intramuscular chondrogenesis. Our findings indicate that these two receptors are important mediators in the response of chondrocytes to changes in the mechanical environment, making them suitable targets for modulating chondrogenesis. Inhibition of TGFβ could also be effective in improving chondrocyte activity in aged or expanded cells that overexpress Alk-1.

Multiplex ALK, RET, and ROS1 fusion mutation detection in FFPE from lung cancer patients by MALDI-TOF mass spectrometry.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13103-e13103
Author(s):  
Kang-Yi Su ◽  
Bing-Ching Ho ◽  
Gee-Chen Chang ◽  
Hsuan-Yu Chen ◽  
Pan-Chyr Yang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Lung Cancer ◽  
High Sensitivity ◽  
Poor Quality ◽  
Lung Cancer Patients ◽  
Maldi Tof Mass Spectrometry ◽  
Anaplastic Lymphoma ◽  
Maldi Tof ◽  
Low Sensitivity ◽  
Alk 5

e13103 Background: Approximately 3-7% of lung tumors harbor anaplastic lymphoma kinase (ALK) fusions in the subgroup of non-small cell lung cancer (NSCLC). In addition to echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion, TRK-fused gene (TFG)-ALK, kinesin family member 5B (KIF5B)-ALK and kinesin light chain 1 (KLC1)-ALK had been reported in lung cancer. On the other hand, RET proto-oncogene (RET) and ROS proto-oncogene 1 (ROS1) fusion proteins also have prevalence in lung cancer. Food and Drug Administration (FDA)-approved several target drugs are available to treat patients with fusion mutations. Therefore, the diagnosis of ALK, RET or ROS1 fusion genes shows quite important. However, nowadays methods of detecting fusions such as fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) are limited to technique, low sensitivity, sample quality as well as subtype classification. Methods: We established nucleotide MALDI-TOF mass spectrometry based multiplex detection platform to distinguish major types including 9 types of EML4-ALK, 5 types of ALK, 5 types of RET and 8 types ROS1 fusions. Results: The detection limitation was about less 1% mutant cells among wild-type cells. In the pilot testing, we used 2 patients’ cell cDNA and 4 patients’ lung FFPE samples cDNA, which had been diagnosed as ALK fusion before, to be detected by this panel, and then identified their variant types successfully. Furthermore, one patient harbored CCDC6-RET fusion mutation was identified by our platform and confirmed by Sanger Sequencing. Conclusions: Taken together, this new panel has high sensitivity and allows little and poor quality samples for detecting. The correlation between clinical characteristics and fusion subtypes can be further investigated by utilizing this platform in the future. Also, the detection panel can be revised based on clinical needs by removing/adding probes.

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