Raf kinase inhibitory protein knockout mice: Expression in the brain and olfaction deficit

Theroux, Steven J.; Pereira, Mandy; Casten, Kimberly S.; Burwell, Rebecca D.; Yeung, Kam C.; Sedivy, John M.; Kłysik, Jan

doi:10.1016/j.brainresbull.2006.11.010

Cited by 58 publications

(71 citation statements)

References 42 publications

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“…The phenotypes of Rkip1 −/− mice described to date include age-dependent learning and olfaction deficits and fertility defects within the males [12,17]. Here we have characterised pancreatic morphology and glucose homeostasis in Rkip1 −/− and provide evidence of a role of RKIP1 as a negative regulator of beta cell mass under physiological (normal growth) and pathological (STZ-induced diabetes) conditions in vivo.…”

Section: Introductionmentioning

confidence: 72%

“…Mouse studies Rkip1 −/− mice were generously provided by Dr Jan Klysik (Brown University, Providence, Rhode Island, USA), maintained in a C57BL/6 background and genotyped as described previously [17]. Protocols were approved by the Animal Ethics Committee of the University of Barcelona and the Principles of Laboratory Animal Care were followed.…”

Section: Methodsmentioning

confidence: 99%

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The role of Raf-1 kinase inhibitor protein in the regulation of pancreatic beta cell proliferation in mice

et al. 2012

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Aims/hypothesis Manoeuvres aimed at increasing beta cell mass have been proposed as regenerative medicine strategies for diabetes treatment. Raf-1 kinase inhibitor protein 1 (RKIP1) is a common regulatory node of the mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) pathways and therefore may be involved in regulation of beta cell homeostasis. The aim of this study was to investigate the involvement of RKIP1 in the control of beta cell mass and function. Methods Rkip1 (also known as Pebp1) knockout (Rkip1 −/− ) mice were characterised in terms of pancreatic and glucose homeostasis, including morphological and functional analysis. Glucose tolerance and insulin sensitivity were examined, followed by assessment of glucose-induced insulin secretion in isolated islets and beta cell mass quantification through morphometry. Further characterisation included determination of endocrine and exocrine proliferation, apoptosis, MAPK activation and whole genome gene expression assays. Capacity to reverse a diabetic phenotype was assessed in adult Rkip1 −/− mice after streptozotocin treatment. Results Rkip1 −/− mice exhibit a moderately larger pancreas and increased beta cell mass and pancreatic insulin content, which correlate with an overall improvement in whole body glucose tolerance. This phenotype is established in young postnatal stages and involves enhanced cellular proliferation without significant alterations in cell death. Importantly, adult Rkip1 −/− mice exhibit rapid reversal of streptozotocin-induced diabetes compared with control mice.Electronic supplementary material The online version of this article (doi:10.1007/s00125-012-2696-9) contains peer-reviewed but unedited supplementary material, which is available to authorised users. Conclusions/interpretation These data implicate RKIP1 in the regulation of pancreatic growth and beta cell expansion, thus revealing RKIP1 as a potential pharmacological target to promote beta cell regeneration.

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Section: Introductionmentioning

confidence: 72%

Section: Methodsmentioning

confidence: 99%

The role of Raf-1 kinase inhibitor protein in the regulation of pancreatic beta cell proliferation in mice

et al. 2012

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“…25 A comprehensive analysis of pebp1 gene expression in the murine brain was performed by Theroux et al using the β-geo reporter. 26 In that study, a gene trap in intron 1 of the murine pebp1 gene resulted in the integration of the β-geo gene cassette, encoding a chimeric protein composed of the enzymes β-galactosidase and neomycin phosphotransferase, downstream of the endogenous pebp1 promoter. X-gal staining in adult mouse brains revealed widespread pebp1 expression with a broad range of intensities (from very weak to strong).…”

Section: Pebp1/rkip: Genomic and Protein Structure Subcellular mentioning

confidence: 99%

“…26,36 In the absence of rkip expression, mice exhibited exaggerated (larger) responses to the clock-delaying andadvancing effects of brief light exposure in the early and late night, respectively. Furthermore, in an experimental model that mimics air travel from Los Angeles to London, rkip-deficient mice required significantly fewer days to readjust their clock to an 8 h advance in the light-dark schedule, suggesting an accelerated recovery from jet lag.…”

Section: Rkip and Entrainment Of The Circadian Clockmentioning

confidence: 99%

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Raf Kinase Inhibitory Protein (RKIP): Functional Pleiotropy in the Mammalian Brain

et al. 2014

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In 1984, a cytosolic protein was isolated from bovine brain and coined phosphatidylethanolamine binding protein (PEBP) to describe its phospholipid-binding potential. Its cellular function remained elusive for more than a decade until it was discovered that PEBP had the ability to suppress the Raf1-mitogen activated protein kinase (MAPK) pathway, earning it the new name of Raf1 kinase inhibitory protein (RKIP). This milestone discovery has paved the way for numerous studies that have now extended the reach of RKIP's function to other signaling cascades, within the context of various physiological and pathophysiological systems. This review will summarize our current knowledge of the neurophysiological roles of RKIP in the mammalian brain, including its function in the circadian clock and synaptic plasticity. It will also discuss evidence for an involvement of RKIP and its derived neuropeptide, hippocampal cholinergic neurostimulating peptide (HCNP), in neural development and differentiation. Implications in certain pathologies such as Alzheimer's disease and brain cancer will be highlighted. By chronicling the diverse functions of RKIP in the brain, we hope that this review will serve as a timely resource that ignites future studies on this versatile, multifaceted protein in the nervous system.

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Raf kinase inhibitor protein1 is a myogenic inhibitor with conserved function in avians and mammals

Coulton

Hou

Mirczuk

et al. 2016

Developmental Dynamics

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Background: Raf Kinase Inhibitor Protein1 (RKIP) is a tumor suppressor that is present in several adult tissues. It functions as an inhibitor of both Raf/Mek/Erk and NFOEB signaling when unphosphorylated, but following phosphorylation the ability to inhibit Raf/Mek/Erk signaling is lost and RKIP becomes an activator of G-protein coupled receptor signaling. In neonates and adults, RKIP is known to be expressed in muscle; however, its physiological function is currently unknown. Results: In this study, we show by in situ hybridization and immunofluorescence that RKIP is also expressed in developing chick embryonic muscle, and mouse C2C12 myoblasts. Furthermore, we demonstrate that, in these systems, it functions as an inhibitor of myogenesis: increased levels of RKIP suppress myotube differentiation whereas decreasing RKIP promotes differentiation. Additionally, we show that the ability of RKIP to inhibit myogenesis is dependent upon its phosphorylation state as only the nonphosphorylated form of RKIP suppresses myogenesis. Conclusions: This study, therefore, clearly demonstrates that RKIP has conserved functions as a myogenic inhibitor in both mammalian and avian muscle. Developmental Dynamics 245:902-912,

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Raf kinase inhibitory protein knockout mice: Expression in the brain and olfaction deficit

Cited by 58 publications

References 42 publications

The role of Raf-1 kinase inhibitor protein in the regulation of pancreatic beta cell proliferation in mice

The role of Raf-1 kinase inhibitor protein in the regulation of pancreatic beta cell proliferation in mice

Raf Kinase Inhibitory Protein (RKIP): Functional Pleiotropy in the Mammalian Brain

Raf kinase inhibitor protein1 is a myogenic inhibitor with conserved function in avians and mammals

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