The Raf‐1 kinase associates with vimentin kinases and regulates the structure of vimentin filaments

Janosch, Petra; Kieser, Arnd; Eulitz, Manfred; Lovrić, Josip; Sauer, Guido; Reichert, Manuela; Gounari, Fotini; Büscher, Dirk; Baccarini, Manuela; Mischak, Harald; Kölch, Walter

doi:10.1096/fj.99-0883com

Cited by 61 publications

(55 citation statements)

References 66 publications

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“…34, No. 6, 2001 Taken together, our results and other accumulating data 14,15,36,37,41,42 raise the question about association of IF with signaling proteins as an important regulator of cell signaling. In this respect, the connection between 14-3-3 and IFs could act as an integrator between structure and signaling.…”

Section: Discussionsupporting

confidence: 59%

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Disturbances in hepatic cell-cycle regulation in mice with assembly-deficient keratins 8/18

et al. 2001

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Simple epithelial tissues such as liver and pancreas express keratins 8 (K8) and 18 (K18) as their major intermediate filament proteins. K8 and K18 null mice and transgenic mice that express mutant K18 (K18C) manifest several hepatocyte abnormalities and demonstrate that K8/18 are important in maintaining liver tissue and cell integrity, although other potential functions remain uncharacterized. Here, we report an additional abnormal liver phenotype, which is similar in K8 null, K18 null, and K18C mouse models. Liver histologic examination showed large polynuclear areas that lacked cell membranes, desmosomal structures, and filamentous actin. Similar, but less prominent, areas were observed in the pancreas. The parenchyma outside the polynuclear areas displayed irregular sinusoidal structures and markedly enlarged nuclei. Most K8 null hepatocytes were positive for the proliferating cell nuclear antigen (PCNA) with a doubled DNA content in comparison with the predominantly PCNA-negative wild-type hepatocytes. The distribution of the 14-3-3 protein was also altered in K8 null mice. Taken together, our results indicate that absence of keratin filaments causes disturbances in cellcycle regulation, driving cells into the S-G2 phase and causing aberrant cytokinesis. These effects could stem from disturbed functions of K8/18-dependent cell-cycle regulators, such as the signaling integrator, 14-3-3. (HEPATOLOGY 2001; 34:1174-1183

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Section: Discussionsupporting

confidence: 59%

“…Vimentin binds to Raf-1, 36 and both vimentin 37 and K18 14,15 bind to 14-3-3. It has also been shown that 14-3-3 proteins, through mitogenactivated protein kinase activation, play a role in efficient induction of keratins in F9 cell differentiation.…”

Section: Discussionmentioning

confidence: 99%

Disturbances in hepatic cell-cycle regulation in mice with assembly-deficient keratins 8/18

et al. 2001

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“…Another example is the observation that Raf-1 can induce the depolymerization of vimentin filaments. This effect is not prevented by MEK inhibitors, and is caused by as yet unknown Raf-1-associated vimentin kinases which are regulated by Raf-1 [134].…”

Section: Signal Diversification : Multi-protein Kinase Complexesmentioning

confidence: 90%

Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions

Kölch

2000

Biochemical Journal

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1,057

118

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The Ras\Raf\MEK (mitogen-activated protein kinase\ERK kinase)\ERK (extracellular-signal-regulated kinase) pathway is at the heart of signalling networks that govern proliferation, differentiation and cell survival. Although the basic regulatory steps have been elucidated, many features of this pathway are only beginning to emerge. This review focuses on the role of protein-protein interactions in the regulation of this pathway, INTRODUCTIONThe mitogen-activated protein kinase (MAPK) pathway is one of the primordial signalling systems that Nature has used in several permutations to accomplish an amazing variety of tasks. It exists in all eukaryotes, and controls such fundamental cellular processes as proliferation, differentiation, survival and apoptosis. The basic arrangement includes a G-protein working upstream of a core module consisting of three kinases : a MAPK kinase kinase (MAPKKK) that phosphorylates and activates a MAPK kinase (MAPKK), which in turn activates MAPK ( Figure 1). This set-up provides not only for signal amplification, but, maybe even more importantly, for additional regulatory interfaces that allow the kinetics, duration and amplitude of the activity to be precisely tuned. At present we can distinguish six MAPK modules, which share structurally related components, but seem to mediate specific biological responses. For recent reviews on MAPK pathways, the reader is referred to references [1][2][3]. Here we will focus on the regulation of the ERK (extracellular-signal-regulated kinase) pathway, which features Ras as G-protein, Raf as MAPKKK, MEK (MAPK\ERK kinase) as MAPKK and ERK as MAPK.Despite enjoying a decade in the limelight of scientific interest and revealing a plethora of new insights into the circuitry of signalling pathways in general, this pathway still holds many secrets. These pertain mainly to the regulation of Raf, and to a deeper understanding of how specific biological responses are encoded by spatial and temporal changes in the activity and subcellular distribution of the pathway components, and how these fluctuations are orchestrated at the molecular level. Work from many laboratories has highlighted protein-protein interactions as powerful means of co-ordinating signalling processes, most strikingly exemplified by the assembly of multi-protein signalling complexes on activated receptors, or of transcriptionfactor complexes on gene promoters. However, it is becoming Abbreviations used : Bcr, Breakpoint cluster region ; BXB, isolated Raf-1 kinase domain ; CNK, connector-enhancer of KSR ; CK2, casein kinase 2 ; CRD, cysteine-rich domain ; DEF, docking site for ERK, FxFP ; DLK, dual leucine-zipper-bearing kinase ; ERK, extracellular-signal-regulated kinase ; Hsp, heat-shock protein ; KIM, kinase interaction motif ; IκB, inhibitor of NF-κB ; JNK, c-Jun N-terminal kinase ; KSR, kinase suppressor of Ras ; MAPK, mitogen-activated protein kinase ; MAPKK, MAPK kinase ; MAPKKK, MAPK kinase kinase ; MEK, MAPK/ERK kinase ; MEKK, MEK kinase ; MP1, MEK partner 1 ; MUK, MAPK upstream kin...

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“…There are many phosphorylation events affecting vimentin. For example, phosphorylation by Raf-1-associated vimentin kinase results in the proper structure of vimentin filaments 50 and phosphorylation by protein kinase C (PKC) creates isoforms that participate in the regulation of organelle movement in melanophores and many signal transduction pathways involving tyrosine kinase, nucleotide exchange factor, serine/threonine kinase, Raf-1, PKC, cytoskeletal protein actin, proteosome component and HSC70 51 . In addition to phosphorylation, the different spots of vimentin seen on the 2-D gel may be due to association with other molecules, such as protein kinase C, integrin or other associated proteins in signal transduction pathways.…”

Section: Discussionmentioning

confidence: 99%

Molecular Profiling of A375 Human Malignant Melanoma Cells Treated with Kojic Acid and Arbutin

Hsieh¹,

Chen²,

Cheng³

2011

Breakthroughs in Melanoma Research

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The Raf‐1 kinase associates with vimentin kinases and regulates the structure of vimentin filaments

Cited by 61 publications

References 66 publications

Disturbances in hepatic cell-cycle regulation in mice with assembly-deficient keratins 8/18

Disturbances in hepatic cell-cycle regulation in mice with assembly-deficient keratins 8/18

Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions

Molecular Profiling of A375 Human Malignant Melanoma Cells Treated with Kojic Acid and Arbutin

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