• Nowadays more than kinases have been identified of

  2024-05-18

  

  Nowadays, more than 500 kinases have been identified of human genome [2]. Imatinib (Gleevec) was the first tyrosine kinase inhibitor approved by the US Food and Drug Administration (FDA) for the treatment of chronic myeloid leukemia [3], and kinases have become an attractive target for the developme

• Phosphoinositide kinase PI K Akt

  2024-05-18

  

  Phosphoinositide 3-kinase (PI3K)/Akt has been well demonstrated in the protection of myocardial cell against IR injury via increasing cardiomyocyte survival, inhibiting excessive autophagy, et al. (Kong et al., 2016). The BMS354825 of ERK1/2 also involves in the regulation of cardiac myocyte surviv

• Afatinib dimaleate A unique finding in this study is that

  2024-05-18

  

  A unique finding in this study is that 12/15-LO influences CREB phosphorylation in the murine brain. While previous reports have found that knockout of 5-lipoxygenase, a related enzyme that also uses arachidonic Afatinib dimaleate for substrate, can regulate CREB phosphoryation in the context of Al

• br Results br Discussion Context specific and dynamic post

  2024-05-18

  

  Results Discussion Context-specific and dynamic post-translational protein modifications are well-established regulators of the signaling pathways that protect eukaryotic DNA integrity during the tremendous task of replication. Advancements in speed, resolution, and sensitivity of MS-based tec

• In this review we will present the traditional

  2024-05-18

  

  In this review, we will present the traditional and actual strategies to study orphan receptors and identify their ligands. An extensive description of the orphan GPCR field has been published in 2013 by Davenport et al. [22]. Therefore, we will focus on the deorphanizations that were reported since

• br Physiology of the apelin pathway br

  2024-05-18

  

  Physiology of the apelin pathway Role of apelin in heart disease Both apelin and apelin receptor null mice manifested moderate reduction in cardiac contractile function under basal conditions and their exercise capacity was markedly reduced (Table 1) [56]. Apelin has direct effects on the prop

• br Apelin Discovered in apelin was initially identified as t

  2024-05-18

  

  Apelin Discovered in 1998, apelin was initially identified as the sole endogenous ligand for the APJ receptor (Tatemoto et al., 1998). Apelin-77 (pre-pro-apelin) is the precursor for various pharmacologically active apelin isoforms (e.g. apelin-12, -13, -17 and 36), and it shares 75–95% sequence

• VEGFR inhibition using sunitinib does not

  2024-05-17

  

  VEGFR2 inhibition using sunitinib does not result in tumor growth reduction or in a further decrease in vessel density in NDRG1 overexpressing glioma rendering these tumors intrinsically resistant to antiangiogenic treatment. Intrinsic resistance to antiangiogenic therapy is defined as a non-respons

• This evidence suggests the strong clinical relevance of

  2024-05-17

  

  This evidence suggests the strong clinical relevance of the identification of acquired resistance mechanisms for a proper therapeutic decision in patients with ALK-rearranged NSCLC. When the tissue is not available, the analysis of circulating tumor DNA (cfDNA) can be a valid alternative for the det

• Cells have developed strategies aiming to enhance both the

  2024-05-17

  

  Cells have developed strategies aiming to enhance both the efficiency of proteins with chaperone activity as well as their overall antioxidant capacity to maintain proteostasis under oxidative stress conditions (Miyata et al., 2012). For instance, 2-Cys peroxiredoxin is an abundantly expressed, anti

• br Downstream signalling of AKT A consensus phosphorylation

  2024-05-17

  

  Downstream signalling of AKT A consensus phosphorylation motif has been described for AKT substrates: R-X-R-X-X-S/T-B where X represents any amino pyruvate dehydrogenase kinase inhibitor and B represents bulky hydrophobic residues (Alessi, Caudwell, Andjelkovic, Hemmings, & Cohen, 1996). Numerou

• DAergic as well as GABAergic and glutamatergic neurons send

  2024-05-17

  

  DAergic, as well as GABAergic and glutamatergic neurons, send projections to target forebrain structures, such as the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC), and support diverse functional roles (Carr and Sesack, 2000a, Carr and Sesack, 2000b, Omelchenko and Sesack, 2009, Taylor

• Role of APPL in endosomal signaling pathways Endosomes consi

  2024-05-17

  

  Role of APPL in endosomal signaling pathways Endosomes consist of distinct membrane subdomains within individual organelles and assist in the translation of extracellular stimuli via cytoplasmic transduction cascades to the nucleus [3], [74]. Endosomal abnormalities are associated with the pathogen

• In eukaryotes class III ACs including

  2024-05-17

  

  In eukaryotes, class III ACs (including GCs) are almost universally present, with the noteworthy exception of higher plants. Our dataset comprises 9690 sequences of class III nucleotide cyclases from 710 eukaryotic species. Approximately 80% thereof belong to subclass IIIa and 10% to subclasses IIIb

• br Acknowledgements We thank Dr Stefan

  2024-05-17

  

  Acknowledgements We thank Dr. Stefan Schulte-Merker and his group members at the Hubrecht Institute (Utrecht, the Netherlands) for their invaluable support of the zebrafish studies. Our work is supported by grants from the Dutch Cancer Society (KWF) and the Netherlands Organisation for Scientific

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