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Richard Blouin - One of the best experts on this subject based on the ideXlab platform.
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The mixed lineage kinase leucine-Zipper protein kinase exhibits a differentiation-associated localization in normal human skin and induces keratinocyte differentiation upon overexpression.
The Journal of investigative dermatology, 2000Co-Authors: Lucie Germain, Julie Fradette, Hubert Robitaille, Rina Guignard, Gilles Grondin, André Nadeau, Richard BlouinAbstract:Leucine-Zipper protein kinase/dual leucine Zipper bearing kinase/mitogen-activated protein kinase-upstream kinase is a recently described protein serine/threonine kinase which belongs to the mixed lineage kinase family. The overall pattern of expression of the leucine-Zipper protein kinase/dual leucine Zipper bearing kinase/mitogen-activated protein kinase-upstream kinase gene in embryonic and adult mouse tissues suggested that this kinase could be involved in the regulation of epithelial cell proliferation and differentiation. In order to get more insights into the potential role of leucine-Zipper protein kinase in these cellular processes, we characterized its expression in normal human skin, both at the mRNA and protein levels. In situ hybridization, western blotting, and indirect immunofluorescence studies were conducted to localize leucine-Zipper protein kinase on various human skin tissues. This is one of the first reports that leucine-Zipper protein kinase has a very precise pattern of expression in human skin epithelia, as both mRNA and protein are restricted to the granular layer of the epidermis and inner root sheath of hair follicles. Detection of leucine-Zipper protein kinase protein on skin from various body sites, donors of different ages as well as on reconstructed human skin always reveals that leucine-Zipper protein kinase is present only in the very differentiated keratinocytes of epidermis and hair follicles. To determine directly whether leucine-Zipper protein kinase exhibits any effect on cell growth and differentiation, keratinocytes were transfected with an expression vector harboring the leucine-Zipper protein kinase cDNA. The presence of this construct in keratinocytes results in growth arrest together with a concomitant increase in filaggrin expression. Collectively, our results indicate that leucine-Zipper protein kinase plays an active part in cellular processes related to terminal differentiation of epidermal keratinocytes.
Michael E Mendelsohn - One of the best experts on this subject based on the ideXlab platform.
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dimerization of cgmp dependent protein kinase 1α and the myosin binding subunit of myosin phosphatase role of leucine Zipper domains
Cellular Signalling, 2003Co-Authors: Howard K Surks, Michael E MendelsohnAbstract:Nitric oxide (NO) and nitrovasodilators induce vascular smooth muscle cell relaxation in part by cGMP-dependent protein kinase (cGK)-mediated activation of myosin phosphatase, which dephosphorylates myosin light chains. We recently found that cGMP-dependent protein kinase 1α binds directly to the myosin-binding subunit (MBS) of myosin phosphatase via the leucine/isoleucine Zipper of cGK. We have now studied the role of the leucine Zipper domain of MBS in dimerization with cGK and the leucine/isoleucine Zipper and leucine Zipper domains of both proteins in homodimerization. Mutagenesis of the MBS leucine Zipper domain disrupts cGKIα-MBS dimerization. Mutagenesis of the MBS leucine Zipper eliminates MBS homodimerization, while similar disruption of the cGKIα leucine/isoleucine Zipper does not prevent formation of cGK dimers. The MBS leucine Zipper domain is phosphorylated by cGK, but this does not have any apparent effect on heterodimer formation between the two proteins. MBS LZ mutants that are unable to bind cGK were poor substrates for cGK. These data support the theory that the MBS leucine Zipper domain is necessary and sufficient to mediate both MBS homodimerization and binding of the protein to cGK. In contrast, the leucine/isoleucine Zipper of cGK is required for binding to MBS, but not for cGK homodimerization. These data support that the MBS and cGK leucine Zipper domains mediate the interaction between these two proteins. The contribution of these domains to both homodimerization and their specific interaction with each other suggest that additional regulatory mechanisms involving these domains may exist.
Terence Tao - One of the best experts on this subject based on the ideXlab platform.
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Interactions between the Leucine-Zipper Motif of cGMP-Dependent Protein Kinase and the C-terminal Region of the Targeting Subunit of Myosin Light Chain Phosphatase
Journal of molecular biology, 2007Co-Authors: Eunhee Lee, Knut Langsetmo, Daivd B. Hayes, Eric J. Sundberg, Terence TaoAbstract:Nitric oxide induces vasodilation by elevating the production of cGMP, an activator of cGMP-dependent protein kinase (PKG). PKG subsequently causes smooth muscle relaxation in part via activation of myosin light chain phosphatase (MLCP). To date, the interaction between PKG and the targeting subunit of MLCP (MYPT1) is not fully understood. Earlier studies by one group of workers showed that the binding of PKG to MYPT1 is mediated by the leucine-Zipper motifs at the N and C termini, respectively, of the two proteins. Another group, however, reported that binding of PKG to MYPT1 did not require the leucine-Zipper motif of MYPT1. In this work we fully characterized the interaction between PKG and MYPT1 using biophysical techniques. For this purpose we constructed a recombinant PKG peptide corresponding to a predicted coiled coil region that contains the leucine-Zipper motif. We further constructed various C-terminal MYPT1 peptides bearing various combinations of a predicted coiled coil region, extensions preceding this coiled coil region, and the leucine-Zipper motif. Our results show, firstly, that while the leucine-Zipper motif at the N terminus of PKG forms a homodimeric coiled coil, the one at the C terminus of MYPT1 is monomeric and non-helical. Secondly, the leucine-Zipper motif of PKG binds to that of MYPT1 to form a heterodimer. Thirdly, when the leucine-Zipper motif of MYPT1 is absent, the PKG leucine-Zipper motif binds to the coiled coil region and upstream segments of MYPT1 via formation of a heterotetramer. These results provide rationalization of some of the findings by others using alternative binding analyses.
Lawrence B Holzman - One of the best experts on this subject based on the ideXlab platform.
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identification of structural and functional domains in mixed lineage kinase dual leucine Zipper bearing kinase required for complex formation and stress activated protein kinase activation
Journal of Biological Chemistry, 2000Co-Authors: Deepak Nihalani, Steven E Merritt, Lawrence B HolzmanAbstract:Abstract Accumulating evidence suggests that mitogen-activated protein kinase signaling pathways form modular signaling complexes. Because the mixed lineage kinase dual leucine Zipper-bearing kinase (DLK) is a large modular protein, structure-function analysis was undertaken to examine the role of DLK domains in macromolecular complex formation. DLK mutants were used to demonstrate that a DLK leucine Zipper-leucine Zipper interaction is necessary for DLK dimerization and to show that DLK dimerization mediated by the leucine Zipper domain is prerequisite for DLK activity and subsequent activation of stress-activated protein kinase (SAPK). Heterologous mixed lineage kinase family members can be co-immunoprecipitated. However, the DLK leucine Zipper domain interacted specifically only with the DLK leucine Zipper domain; in contrast, DLK NH2-terminal region was sufficient to co-immunoprecipitate leucine Zipper kinase and DLK. DLK has been shown to associate with the putative scaffold protein JIP1. This association occurred through the DLK NH2-terminal region and occurred independently of DLK catalytic activity. Although the DLK NH2-terminal region associated directly with JIP-1, this region did not interact directly with either DLK or leucine Zipper kinase. Therefore, DLK may interact with heterologous mixed lineage kinase proteins via intermediary proteins. The NH2-terminal region of overexpressed DLK was required for activation of SAPK. These results provide evidence that protein complex formation is required for signal transduction from DLK to SAPK.
John B E Burch - One of the best experts on this subject based on the ideXlab platform.
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chicken vitellogenin gene binding protein a leucine Zipper transcription factor that binds to an important control element in the chicken vitellogenin ii promoter is related to rat dbp
Molecular and Cellular Biology, 1991Co-Authors: S V Iyer, D L Davis, S N Seal, John B E BurchAbstract:We screened a chicken liver cDNA expression library with a probe spanning the distal region of the chicken vitellogenin II (VTGII) gene promoter and isolated clones for a transcription factor that we have named VBP (for vitellogenin gene-binding protein). VBP binds to one of the most important positive elements in the VTGII promoter and appears to play a pivotal role in the estrogen-dependent regulation of this gene. The protein sequence of VBP was deduced from a nearly full length cDNA copy and was found to contain a basic/Zipper (bZIP) motif. As expected for a bZIP factor, VBP binds to its target DNA site as a dimer. Moreover, VBP is a stable dimer free in solution. A data base search revealed that VBP is related to rat DBP. However, despite the fact that the basic/hinge regions of VBP and DBP differ at only three amino acid positions, the DBP binding site in the rat albumin promoter is a relatively poor binding site for VBP. Thus, the optimal binding sites for VBP and DBP may be distinct. Similarities between the VBP and DBP leucine Zippers are largely confined to only four of the seven helical spokes. Nevertheless, these leucine Zippers are functionally compatible and appear to define a novel subfamily. In contrast to the bZIP regions, other portions of VBP and DBP are markedly different, as are the expression profiles for these two genes. In particular, expression of the VBP gene commences early in liver ontogeny and is not subject to circadian control.
