1,721,017 research outputs found
The KDEL receptor: New functions for an old protein
No full textThe KDEL receptor is a seven-transmembrane-domain protein that was first described about 20 years ago. Its well-known function is to retrotransport chaperones from the Golgi complex to the endoplasmic reticulum. Recent studies, however, have suggested that the KDEL receptor has additional functions. Indeed, we have demonstrated that chaperone-bound KDEL receptor triggers the activation of Src family kinases on the Golgi complex. This activity is essential in the regulation of Golgi-to-plasma membrane transport. However, the identification of different KDEL receptor interactors that are inconsistent with these established functions opens the possibility of further receptor activities
The physiology of membrane transport and endomembrane-based signalling
No full textSome of the important open questions concerning the physiology of the secretory pathway relate to its homeostasis. Secretion involves a number of separate compartments for which their transport activities should be precisely cross-coordinated to avoid gross imbalances in the trafficking system. Moreover, the membrane fluxes across these compartments should be able to adapt to environmental 'requests' and to respond to extracellular signals. How is this regulation effected? Here, we consider evidence that endomembrane-based signalling cascades that are similar in organization to those used at the plasma membrane coordinate membrane traffic. If this is the case, this would also represent a model for a more general inter-organelle signalling network for functionally interconnecting different intracellular activities, a necessity for the maintenance of cellular homeostasis and to express harmonic global cellular responses
Comparative analysis of beta-adrenergic receptor kinase and beta-arrestin mRNA expression in human cells.
No full textReceptor phosphorylation is a key step in the process of rapid desensitization. beta-Adrenergic receptor kinase is a specific receptor kinase that is known to phosphorylate and induce desensitization of several G-coupled synaptic receptors only when they are occupied by their agonists. We recently cloned human beta ARK cDNA and reported high levels of beta ARK expression in human peripheral blood leukocytes, also providing the first evidence for its possible functional role in these cells. Complete homologous receptor desensitization by beta ARK requires an additional cytosolic factor, called beta-arrestin. In the present study, we have cloned a 212 bp fragment of the human beta-arrestin cDNA to perform a comparative analysis of beta ARK and beta-arrestin mRNA expression in various human cell types. We found that also beta-arrestin mRNA is abundant in non-innervated tissues and cells. The fact that the entire machinery for G-coupled receptor desensitization is highly expressed in these cells further supports the idea that beta ARK may regulate nonsynaptic as well as synaptic receptors
Molecular cloning, functional expression and mRNA analysis of human beta-adrenergic receptor kinase 2.
No full textIn the present study the cDNA of human beta ARK2 was cloned using both PCR and cDNA library screening, subcloned into an expression vector and transiently expressed in COS7 cells. The expressed kinase activity was approximately 40% as efficient as human beta ARK1 in phosphorylating bovine rod outer segments in vitro. Northern blot analysis of human and bovine mRNA revealed a species-specific pattern of multiple hybridization bands, with two major transcripts in human rather than one in bovine. High levels of mRNA expression were found in peripheral blood leukocytes
G protein-coupled receptors: Heterologous regulation of homologous desensitization and its implications
No full textTwo patterns of rapid desensitization have been characterized for G protein-coupled receptors: homologous desensitization, which mainly involves G protein-coupled receptor kinases and arrestins, and heterologous desensitization, which mainly involves protein kinases A (PKA) and C (PKC). In this review, Tsu Tshen Chuang and colleagues discuss evidence to show that PKA and PKC can modify the functional state of the G protein-coupled receptor kinases/arrestin homologous desensitization machinery, providing a novel level of cross-talk in signal transduction. Studies on regulation of G protein-coupled receptor kinases and arrestins confirm that the functional state of this machinery may have important consequences for cellular responsiveness and may represent new targets for therapeutic strategies
GENE EXPRESSION SIGNATURES DIFFERENTIATE NON-CELIAC GLUTEN SENSITIVITY FROM CELIAC DISEASE PATIENTS AND CONTROLS AND MAY POTENTIALLY CONTRIBUTE TO DISEASE DIAGNOSIS
No full textNeuroprotective modulation of the unfolded protein response in Marinesco-Sjögren syndrome: PERK signaling inhibition and beyond
No full textRegulation of G protein-coupled receptor kinase subtypes in activated T lymphocytes. Selective increase of beta-adrenergic receptor kinase 1 and 2.
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