Urea signaling in cultured murine inner medullary collecting duct (mIMCD3) cells involves protein kinase C, inositol 1,4,5-trisphosphate (IP3), and a putative receptor tyrosine kinase.

Cohen, David; Gullans, Steven R.; Chin, William W.

doi:10.1172/jci118619

Cited by 51 publications

(44 citation statements)

References 41 publications

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“…3A). PKC and NF-kB signaling pathways have been demonstrated to be activated in cells cultured in medium containing high glucose (6, 7), high albumin (8), or high urea (27). However, calphostin C (a PKC inhibitor) and PDTC (an NF-kB inhibitor) showed no apparent inhibition of NaCl-induced MCP1 mRNA expression in NRK52E cells (Fig.…”

Section: Signaling Pathways Participating In Induction Of Mcp1 Expresmentioning

confidence: 96%

Hypertonicity-Induced Expression of Monocyte Chemoattractant Protein-1 through a Novel Cis-Acting Element and MAPK Signaling Pathways

Kojima

Taniguchi

Tsuzuki

et al. 2010

The Journal of Immunology

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MCP1 is upregulated by various stimuli, including LPS, high glucose, and hyperosmolality. However, the molecular mechanisms of transcriptional regulation of the MCP1 gene under hyperosmolar conditions are poorly understood. Treatment of NRK52E cells with NaCl or mannitol resulted in significant elevation of MCP1 mRNA and protein in a time- and dose-dependent manner. Treatment with a p38MAPK inhibitor (SB203580), an ERK inhibitor (PD98059), or an MEK inhibitor (U0126), suppressed the increase in MCP1 expression caused by hypertonic NaCl, whereas a JNK inhibitor (SP600125) and an AP1 inhibitor (curcumin) failed to attenuate MCP1 mRNA expression by NaCl. In the 5′-flanking region of the MCP1 gene, there is a sequence motif similar to the consensus TonE/ORE as well as the consensus C/E binding protein (BP), NF-κB, and AP1/Sp1 sites. Luciferase activity in cells transfected with reporter constructs containing a putative TonE/ORE element (MCP1-TonE/ORE) enhanced reporter gene expression under hypertonic stress. Results of electrophoretic gel mobility shift assay showed a slow migration of the MCP1-TonE/ORE probe, representing the binding of TonEBP/OREBP/NFAT5 to this enhancer element. These results indicate that the 5′-flanking region of MCP1 contains a hypertonicity-sensitive cis-acting element, MCP1-TonE/ORE, as a novel element in the MCP1 gene. Furthermore, p38MAPK and MEK–ERK pathways appear to be, at least in part, involved in hypertonic stress-mediated regulation of MCP1 expression through the MCP1-TonE/ORE.

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Section: Signaling Pathways Participating In Induction Of Mcp1 Expresmentioning

confidence: 96%

Hypertonicity-Induced Expression of Monocyte Chemoattractant Protein-1 through a Novel Cis-Acting Element and MAPK Signaling Pathways

Kojima

Taniguchi

Tsuzuki

et al. 2010

The Journal of Immunology

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“…The intracellular content of PIPs is known to be altered by osmotic swelling [31,32]. To investigate whether the localization of CERK changes in response to PI(4,5)P 2 elevation, we examined GFP-tagged CERK (GFP-CERK) or ΔPH-CERK (GFP-ΔPH-CERK) in transfected COS7 cells under hyper-osmotic conditions.…”

Section: Hyper-osmotic Stress Induces the Translocation Of Cerk To Thmentioning

confidence: 99%

The interaction between the pleckstrin homology domain of ceramide kinase and phosphatidylinositol 4,5-bisphosphate regulates the plasma membrane targeting and ceramide 1-phosphate levels

Kim

Mitsutake

Igarashi

2006

Biochemical and Biophysical Research Communications

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Ceramide kinase (CERK) converts ceramide (Cer) to ceramide-1-phosphate (C1P), which has recently emerged as a new bioactive molecule capable of regulating diverse cellular functions. The N-terminus of the CERK protein encompasses a sequence motif known as a pleckstrin homology (PH) domain. Although the PH domain was previously demonstrated to be an important domain for the subcellular localization of CERK, the precise properties of this domain remained unclear. In this study, we reveal that the PH domain of CERK exhibits high affinity for phosphatidylinositol (4,5) bisphosphate (PI(4,5)P 2 ) [0], among other lipids. Furthermore, in COS7 cells, GFPfused CERK translocated rapidly from the cytoplasm to the plasma membrane in response to hyper-osmotic stress, which is known to increase the intracellular PI(4,5)P 2 levels, whereas a PH-domain deletion mutant did not. Additionally, in Sphingolipids are ubiquitous constituents of eukaryotic cells that have essential roles in cell growth, survival and death [1,2]. Their metabolites such as sphingosine (Sph), sphingosine 1-phosphate (S1P), ceramide (Cer), and ceramide 1-phosphate (C1P) are involved in signaling pathways that control various cell functions [3,4,5]. For instance Cer, the precursor for all sphingolipids, functions as a second messenger in a variety of cellular events including apoptosis and cell differentiation [6]. Cer can be also phosphorylated into C1P by Cer kinase (CERK) [7].CERK activity was first identified in brain synaptic vesicles by Bajjalieh and coworkers [8], and was subsequently found in human leukemia (HL-60) cells [9]. A decade later, CERK was cloned based on its sequence homology to sphingosine kinase (SPHK) type 1 [10]. Both C1P and CERK have been implicated in the regulation of vital cellular processes, such as cell proliferation [11,12], apoptosis [13], phagocytosis [14,15] and inflammation [16,17]. Recently, we demonstrated that CERK and C1P are required for the degranulation process in mast cells [18], and that this process is dependent on calmodulin [19].Although it shares sequence homology with SPHKs, CERK differs significantly in its N-terminus. The N-terminus of CERK is myristoylated [20], which has little apparent effect on localization or enzyme activity [20], and contains a 5 pleckstrin homology (PH) domain [10]. The PH domain, a 120-amino acid residue stretch originally identified in pleckstrin but found in over 100 diverse proteins, has been the focus of extensive structural and functional studies [21][22][23][24]. Very recently, we demonstrated that the PH domain of CERK, especially the Leu10 residue, is not only indispensable for the enzyme's activity but also acts as a regulator of that activity [25].To date, however, the precise target and roles of the PH domain in CERK have not been well characterized.Most PH domain-containing proteins can bind with high specificity and affinity Materials and methods Cell culture and transfectionCOS7 and HEK293 cells were obtained from ATCC. Cells were maintained on collagen-coat...

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“…Detergent lysates were prepared, subjected to electrophoresis, and transferred to polyvinylidinedifluoride, as previously described (12). Equal amounts of protein [in µg; quantitated via the D C assay (Bio-Rad) according to the manufacturer's directions] were loaded per gel lane.…”

Section: And References Therein)mentioning

confidence: 99%

Hypotonicity activates transcription through ERK-dependent and -independent pathways in renal cells

Zhang

Yang

Cohen

1998

American Journal of Physiology-Cell Physiology

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Hypotonicity activates transcription through ERK-dependent and -independent pathways in renal cells. Am. J. Physiol. 275 (Cell Physiol. 44): C1104-C1112, 1998.-Acute hypotonic shock (50% dilution of medium with sterile water, but not with isotonic NaCl) activated the extracellular signal response kinase (ERK) mitogen-activated protein (MAP) kinases in renal medullary cells, as measured by Western analysis with a phospho-ERK-specific antibody and by in vitro kinase assay of epitope-tagged ERKs immunoprecipitated from stable HA-ERK transfectants. Hypotonicity also activated the transcription factor and ERK substrate Elk-1 in a partially PD-98059-sensitive fashion, as assessed by chimeric reporter gene assay. Consistent with these data, hypotonic stress activated transcription of the immediate-early gene transcription factor Egr-1 in a partially PD-98059-sensitive fashion. Hypotonicity-inducible Egr-1 transcription was mediated in part through 5Ј-flanking regions containing serum response elements and in part through the minimal Egr-1 promoter. Elimination of the Ets motifs adjacent to key regulatory serum response elements in the Egr-1 promoter diminished the effect of hypotonicity but failed to abolish it. Interestingly, hypotonicity also transiently activated p38 and c-Jun NH 2 -terminal kinase 1, as determined by immunoblotting with anti-phospho-MAP kinase antibodies. Taken together, these data strongly suggest that hypotonicity activates immediate-early gene transcription in renal medullary cells via MAP kinase kinase-dependent and -independent mechanisms. urea; kidney; signal transduction; p38; stress-activated protein kinase; c-Jun amino-terminal kinase ALTHOUGH UBIQUITOUS among prokaryotes and simple eukaryotes, exposure to hypotonicity in higher eukaryotes is generally limited to relatively few epithelia in the absence of systemic disturbances in water balance. In response to water loading or diuresis, cells of the renal medulla encounter a markedly hypotonic milieu (20). In addition, the total solute concentration of a markedly hypertonic renal medullary interstitium, achievable in the face of avid water conservation and comprising a total solute burden Ͼ2,000 mosM, may fall by Ͼ50% in Ͻ1 h after diuresis (5). In response to such physiological anisotonicity, cell volume is acutely regulated through rapid influx or efflux of inorganic ions (e.g., K ϩ and Cl Ϫ ). Thereafter, accumulation or dumping of osmotically active organic solutes called osmolytes ensues (20). In aggregate, these sequential mechanisms achieve the regulatory volume decrease (RVD) essential for maintenance of cell integrity in response to hypotonicity.The molecular mechanisms underlying RVD have received increasing attention; inorganic ion and organic solute efflux pathways have been characterized. Swelling-responsive inorganic ion currents have been observed in diverse systems from prokaryotes to mammalian cells (reviewed in Ref. 8). Among renal epithelia, Cl Ϫ and cation currents have been detected in cells of the proximal tubule (62)...

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Urea signaling in cultured murine inner medullary collecting duct (mIMCD3) cells involves protein kinase C, inositol 1,4,5-trisphosphate (IP3), and a putative receptor tyrosine kinase.

Cited by 51 publications

References 41 publications

Hypertonicity-Induced Expression of Monocyte Chemoattractant Protein-1 through a Novel Cis-Acting Element and MAPK Signaling Pathways

Hypertonicity-Induced Expression of Monocyte Chemoattractant Protein-1 through a Novel Cis-Acting Element and MAPK Signaling Pathways

The interaction between the pleckstrin homology domain of ceramide kinase and phosphatidylinositol 4,5-bisphosphate regulates the plasma membrane targeting and ceramide 1-phosphate levels

Hypotonicity activates transcription through ERK-dependent and -independent pathways in renal cells

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