![]() J Biol Chem 275: 16466–16472.īowman AB, Kamal A, Ritchings BW, Philp AV, McGrail M, Gindhart JG et al. IB1 reduces cytokine-induced apoptosis of insulin-secreting cells. J Biol Chem 273: 1843–1846.īonny C, Oberson A, Steinmann M, Schorderet DF, Nicod P, Waeber G. IB1, a JIP-1-related nuclear protein present in insulin-secreting cells. Bioessays 28: 923–934.īonny C, Nicod P, Waeber G. The isoform-specific functions of the c-Jun N-terminal Kinases (JNKs): differences revealed by gene targeting. Counting on mitogen-activated protein kinases-ERKs 3, 4, 5, 6, 7 and 8. KSR-1 binds to G-protein βγ subunits and inhibits βγ-induced mitogen-activated protein kinase activation. Biochem Biophys Res Commun 293: 647–652.īell B, Xing H, Yan K, Gautam N, Muslin AJ. Phospholipase C-beta 2 interacts with mitogen-activated protein kinase kinase 3. This review focuses on defining the diverse mechanisms by which these scaffold proteins interact with their respective MAPK modules and the role of such interactions in the spatiotemporal organization as well as context-specific signaling of the different MAPK modules.īarr AJ, Marjoram R, Xu J, Snyderman R. The scaffold proteins themselves are finely regulated resulting in dynamic intra- and inter-molecular interactions that can modulate the signaling outputs of MAPK modules. Scaffold proteins play a determinant role in modulating the signaling strength of their cognate MAPK module by regulating the signal amplitude and duration. By linking the MAP3K, MAP2K and MAPK into a multienzyme complex, these MAPK-specific scaffold proteins provide an insulated physical conduit through which signals from the respective MAPK can be transmitted to the appropriate spatiotemporal cellular loci. Recent studies have shown that a novel class of scaffold proteins mediates the structural and functional organization of the three-tier MAPK module. The AKAP transduceosome thus optimizes the amplitude and the signal/noise ratio of cAMP-PKA stimuli travelling from the membrane to the nucleus and other subcellular compartments.Mitogen-activated protein kinases (MAPKs) regulate critical signaling pathways involved in cell proliferation, differentiation and apoptosis. ![]() The transduceosome amplifies cAMP and other signals locally and, by stabilizing and reducing the basal activity of PKA, it also exerts long-distance effects. Although AKAPs have been identified on the basis of their interaction with PKA, they also bind other signaling molecules, mainly phosphatases and kinases, that regulate AKAP targeting and activate other signal transduction pathways.We suggest that AKAP forms a “transduceosome” by acting as an autonomous multivalent scaffold that assembles and integrates signals derived from multiple pathways. Alternative splicing can shuffle targeting and tethering domains to generate a variety of AKAPs with different targeting specificity. Localization recruits protein kinase A (PKA) holoenzyme close to its substrate/effector proteins, directing and amplifying the biological effects of cAMP signaling.AKAPs include two conserved structural modules: (i) a targeting domain that serves as a scaffold and membrane anchor and (ii) a tethering domain that interacts with PKA regulatory subunits. CAMP-dependent protein kinase is targeted to discrete subcellular locations by a family of specific anchor proteins (A-kinase anchor proteins, AKAPs). ![]()
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