LIVIVO - Search results -

Search results

Result 1 - 10 of total 35

Search options

Article ; Online: Abnormal expression of long non-coding RNAs RMRP, CTC-487M23.5, and DGCR5 in the peripheral blood of patients with Bipolar disorder.

Ghamari, Melina / Mehrab Mohseni, Mahdieh / Taheri, Mohammad / Neishabouri, Seyedeh Morvarid / Shirvani-Farsani, Zeinab

2023 Volume 39, Issue 2, Page(s) 313–320

Abstract: Long non-coding RNAs (lncRNAs) have been recently considered as one of the regulatory mechanisms of the nervous system. Hence, lncRNAs may be considered diagnostic biomarkers for bipolar disorder (BD). We aimed to investigate the expression of RMRP, CTC- ... ...

Abstract	Long non-coding RNAs (lncRNAs) have been recently considered as one of the regulatory mechanisms of the nervous system. Hence, lncRNAs may be considered diagnostic biomarkers for bipolar disorder (BD). We aimed to investigate the expression of RMRP, CTC-487M23.5, and DGCR5 lncRNAs in bipolar patients. The levels of these three lncRNAs were measured in peripheral blood mononuclear cells (PBMCs) of 50 BD patients and 50 healthy subjects by real-time PCR. Moreover, we performed a ROC curve analysis between the gene expression and some clinical features of BD patients. Significant upregulation of RMRP and CTC-487M23.5 and no significant change in levels of DGCR5 was observed in BD individuals compared with controls. Also, we found upregulation of RMRP and downregulation of CTC-487M23.5 and DGCR5 in females with BD. The areas under the ROC curve (AUC) for RMRP and CTC-487M23.5 lncRNAs were 0.80 and 0.61, respectively. There was no significant correlation between the expression of these three lncRNAs and clinical features in PBMCs of BD patients. These results suggest a role for RMRP and CTC-487M23.5 in the pathogenesis of bipolar disorder. Moreover, the peripheral expression of these two lncRNAs might be beneficial as potential biomarkers for BD.
MeSH term(s)	Female ; Humans ; Biomarkers/metabolism ; Bipolar Disorder/genetics ; Down-Regulation ; Leukocytes, Mononuclear/metabolism ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism
Chemical Substances	Biomarkers ; RMRP non-coding RNA, human ; RNA, Long Noncoding ; long noncoding RNA DGCR5, human
Language	English
Publishing date	2023-11-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	632824-6
ISSN	1573-7365 ; 0885-7490
ISSN (online)	1573-7365
ISSN	0885-7490
DOI	10.1007/s11011-023-01316-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2155: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Deregulation of NF-κB associated long non-coding RNAs in bipolar disorder.

Pirbalouti, Razieh Ghasemi / Mohseni, Mahdieh Mehrab / Taheri, Mohammad / Neishabouri, Seyedeh Morvarid / Shirvani-Farsani, Zeinab

Metabolic brain disease

2023 Volume 38, Issue 7, Page(s) 2223–2230

Abstract: Long non-coding RNAs (lncRNAs) are major genetic factors whose disruption lead to many diseases, including nervous system diseases. Bipolar disorder (BD) is a neuro-psychiatric disease with no definitive diagnosis and incomplete treatment. Regarding the ... ...

Abstract	Long non-coding RNAs (lncRNAs) are major genetic factors whose disruption lead to many diseases, including nervous system diseases. Bipolar disorder (BD) is a neuro-psychiatric disease with no definitive diagnosis and incomplete treatment. Regarding the role of NF-κB-associated lncRNAs in the neuro-psychiatric disorders, we examined the expression of three lncRNAs, DICER1-AS1, DILC, and CHAST, in BD patients. To assess lncRNA expression in peripheral blood mononuclear cells (PBMCs) of 50 BD patients and 50 healthy individuals, Real-time PCR was used. Additionally, some clinical characteristics of BD patients were investigated via an analysis of ROC curves and correlations. Based on our results, the expression level of CHAST increased significantly in BD patients in comparison with healthy people, in BD men compared with healthy men, as well as in BD women in comparison with control females (p < 0.05). A similar increase in expression was observed for DILC and DICER1-AS1 lncRNAs in female patients compared with healthy women. Whereas compared to healthy men, DILC was decreased in diseased men. Based on the results of the ROC curve, the area under the curve (AUC) for CHAST lncRNA was 0.83 with a P value of 0.0001. So, the expression level of CHAST lncRNA could play a role in the pathobiology of the BD and be considered a good putative biomarker for individuals with bipolar disorder.
MeSH term(s)	Male ; Humans ; Female ; NF-kappa B/metabolism ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; Bipolar Disorder/genetics ; Bipolar Disorder/metabolism ; Leukocytes, Mononuclear/metabolism ; Biomarkers ; Ribonuclease III/metabolism ; DEAD-box RNA Helicases/metabolism
Chemical Substances	NF-kappa B ; RNA, Long Noncoding ; Biomarkers ; DICER1 protein, human (EC 3.1.26.3) ; Ribonuclease III (EC 3.1.26.3) ; DEAD-box RNA Helicases (EC 3.6.4.13)
Language	English
Publishing date	2023-06-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	632824-6
ISSN	1573-7365 ; 0885-7490
ISSN (online)	1573-7365
ISSN	0885-7490
DOI	10.1007/s11011-023-01246-y
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 2155: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: PI3K inhibition circumvents resistance to SHP2 blockade in metastatic triple-negative breast cancer.

Amante, Romain J / Jehanno, Charly / De Silva, Duvini / Coissieux, Marie-May / Ackerknecht, Markus / Romanet, Vincent / Sethi, Atul / Hamelin, Baptiste / Preca, Bogdan-Tiberius / Piscuoglio, Salvatore / Ng, Charlotte K Y / Mohseni, Morvarid / Bentires-Alj, Mohamed

Journal of mammary gland biology and neoplasia

2023 Volume 28, Issue 1, Page(s) 13

Abstract: The protein tyrosine phosphatase SHP2 activates oncogenic pathways downstream of most receptor tyrosine kinases (RTK) and has been implicated in various cancer types, including the highly aggressive subtype of triple-negative breast cancer (TNBC). ... ...

Abstract	The protein tyrosine phosphatase SHP2 activates oncogenic pathways downstream of most receptor tyrosine kinases (RTK) and has been implicated in various cancer types, including the highly aggressive subtype of triple-negative breast cancer (TNBC). Although allosteric inhibitors of SHP2 have been developed and are currently being evaluated in clinical trials, neither the mechanisms of the resistance to these agents, nor the means to circumvent such resistance have been clearly defined. The PI3K signaling pathway is also hyperactivated in breast cancer and contributes to resistance to anticancer therapies. When PI3K is inhibited, resistance also develops for example via activation of RTKs. We therefore assessed the effect of targeting PI3K and SHP2 alone or in combination in preclinical models of metastatic TNBC. In addition to the beneficial inhibitory effects of SHP2 alone, dual PI3K/SHP2 treatment decreased primary tumor growth synergistically, blocked the formation of lung metastases, and increased survival in preclinical models. Mechanistically, transcriptome and phospho-proteome analyses revealed that resistance to SHP2 inhibition is mediated by PDGFRβ-evoked activation of PI3K signaling. Altogether, our data provide a rationale for co-targeting of SHP2 and PI3K in metastatic TNBC.
MeSH term(s)	Humans ; Triple Negative Breast Neoplasms/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphatidylinositol 3-Kinases/pharmacology ; Phosphatidylinositol 3-Kinases/therapeutic use ; Signal Transduction ; Cell Line, Tumor
Chemical Substances	Phosphatidylinositol 3-Kinases (EC 2.7.1.-)
Language	English
Publishing date	2023-06-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1327345-0
ISSN	1573-7039 ; 1083-3021
ISSN (online)	1573-7039
ISSN	1083-3021
DOI	10.1007/s10911-023-09539-9
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 4478: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: SHP2 inhibition reduces leukemogenesis in models of combined genetic and epigenetic mutations.

Pandey, Ruchi / Ramdas, Baskar / Wan, Changlin / Sandusky, George / Mohseni, Morvarid / Zhang, Chi / Kapur, Reuben

The Journal of clinical investigation

2019 Volume 129, Issue 12, Page(s) 5468–5473

Abstract: In patients with acute myeloid leukemia (AML), 10% to 30% with the normal karyotype express mutations in regulators of DNA methylation, such as TET2 or DNMT3A, in conjunction with activating mutation in the receptor tyrosine kinase FLT3. These patients ... ...

Abstract	In patients with acute myeloid leukemia (AML), 10% to 30% with the normal karyotype express mutations in regulators of DNA methylation, such as TET2 or DNMT3A, in conjunction with activating mutation in the receptor tyrosine kinase FLT3. These patients have a poor prognosis because they do not respond well to established therapies. Here, utilizing mouse models of AML that recapitulate cardinal features of the human disease and bear a combination of loss-of-function mutations in either Tet2 or Dnmt3a along with expression of Flt3ITD, we show that inhibition of the protein tyrosine phosphatase SHP2, which is essential for cytokine receptor signaling (including FLT3), by the small molecule allosteric inhibitor SHP099 impairs growth and induces differentiation of leukemic cells without impacting normal hematopoietic cells. We also show that SHP099 normalizes the gene expression program associated with increased cell proliferation and self-renewal in leukemic cells by downregulating the Myc signature. Our results provide a new and more effective target for treating a subset of patients with AML who bear a combination of genetic and epigenetic mutations.
MeSH term(s)	Animals ; DNA (Cytosine-5-)-Methyltransferases/genetics ; DNA Methylation ; DNA-Binding Proteins/genetics ; Humans ; Leukemia, Myeloid, Acute/drug therapy ; Mice ; Mutation ; Piperidines/pharmacology ; Piperidines/therapeutic use ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/antagonists & inhibitors ; Proto-Oncogene Proteins/genetics ; Pyrimidines/pharmacology ; Pyrimidines/therapeutic use ; fms-Like Tyrosine Kinase 3/genetics
Chemical Substances	DNA-Binding Proteins ; Piperidines ; Proto-Oncogene Proteins ; Pyrimidines ; SHP099 ; Tet2 protein, mouse (EC 1.13.11.-) ; DNA (Cytosine-5-)-Methyltransferases (EC 2.1.1.37) ; DNA methyltransferase 3A (EC 2.1.1.37) ; Flt3 protein, mouse (EC 2.7.10.1) ; fms-Like Tyrosine Kinase 3 (EC 2.7.10.1) ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 (EC 3.1.3.48)
Language	English
Publishing date	2019-11-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI130520
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ua VI Zs.184: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Resistance to allosteric SHP2 inhibition in FGFR-driven cancers through rapid feedback activation of FGFR.

Lu, Hengyu / Liu, Chen / Huynh, Hung / Le, Thi Bich Uyen / LaMarche, Matthew J / Mohseni, Morvarid / Engelman, Jeffrey A / Hammerman, Peter S / Caponigro, Giordano / Hao, Huai-Xiang

Oncotarget

2020 Volume 11, Issue 3, Page(s) 265–281

Abstract: SHP2 mediates RAS activation downstream of multiple receptor tyrosine kinases (RTKs) and cancer cell lines dependent on RTKs are in general dependent on SHP2. Profiling of the allosteric SHP2 inhibitor SHP099 across cancer cell lines harboring various ... ...

Abstract	SHP2 mediates RAS activation downstream of multiple receptor tyrosine kinases (RTKs) and cancer cell lines dependent on RTKs are in general dependent on SHP2. Profiling of the allosteric SHP2 inhibitor SHP099 across cancer cell lines harboring various RTK dependencies reveals that FGFR-dependent cells are often insensitive to SHP099 when compared to EGFR-dependent cells. We find that FGFR-driven cells depend on SHP2 but exhibit resistance to SHP2 inhibitors
Language	English
Publishing date	2020-01-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.27435
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Time-resolved phosphoproteomics reveals scaffolding and catalysis-responsive patterns of SHP2-dependent signaling.

Vemulapalli, Vidyasiri / Chylek, Lily A / Erickson, Alison / Pfeiffer, Anamarija / Gabriel, Khal-Hentz / LaRochelle, Jonathan / Subramanian, Kartik / Cao, Ruili / Stegmaier, Kimberley / Mohseni, Morvarid / LaMarche, Matthew J / Acker, Michael G / Sorger, Peter K / Gygi, Steven P / Blacklow, Stephen C

eLife

2021 Volume 10

Abstract: SHP2 is a protein tyrosine phosphatase that normally potentiates intracellular signaling by growth factors, antigen receptors, and some cytokines, yet is frequently mutated in human cancer. Here, we examine the role of SHP2 in the responses of breast ... ...

Abstract	SHP2 is a protein tyrosine phosphatase that normally potentiates intracellular signaling by growth factors, antigen receptors, and some cytokines, yet is frequently mutated in human cancer. Here, we examine the role of SHP2 in the responses of breast cancer cells to EGF by monitoring phosphoproteome dynamics when SHP2 is allosterically inhibited by SHP099. The dynamics of phosphotyrosine abundance at more than 400 tyrosine residues reveal six distinct response signatures following SHP099 treatment and washout. Remarkably, in addition to newly identified substrate sites on proteins such as occludin, ARHGAP35, and PLCγ2, another class of sites shows reduced phosphotyrosine abundance upon SHP2 inhibition. Sites of decreased phospho-abundance are enriched on proteins with two nearby phosphotyrosine residues, which can be directly protected from dephosphorylation by the paired SH2 domains of SHP2 itself. These findings highlight the distinct roles of the scaffolding and catalytic activities of SHP2 in effecting a transmembrane signaling response.
MeSH term(s)	Catalysis ; Cell Line, Tumor ; Epidermal Growth Factor/metabolism ; ErbB Receptors/metabolism ; Guanine Nucleotide Exchange Factors/metabolism ; Humans ; Occludin/metabolism ; Phospholipase C gamma/metabolism ; Phosphoproteins/metabolism ; Phosphorylation ; Phosphotyrosine/metabolism ; Piperidines/metabolism ; Piperidines/pharmacology ; Protein Binding ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/metabolism ; Proteomics/methods ; Pyrimidines/metabolism ; Pyrimidines/pharmacology ; Repressor Proteins/metabolism ; Signal Transduction/drug effects ; src Homology Domains
Chemical Substances	ARHGAP35 protein, human ; Guanine Nucleotide Exchange Factors ; Occludin ; Phosphoproteins ; Piperidines ; Pyrimidines ; Repressor Proteins ; SHP099 ; Phosphotyrosine (21820-51-9) ; Epidermal Growth Factor (62229-50-9) ; ErbB Receptors (EC 2.7.10.1) ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 (EC 3.1.3.48) ; Phospholipase C gamma (EC 3.1.4.3)
Language	English
Publishing date	2021-03-23
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.64251
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Time-resolved phosphoproteomics reveals scaffolding and catalysis-responsive patterns of SHP2-dependent signaling

Vidyasiri Vemulapalli / Lily A Chylek / Alison Erickson / Anamarija Pfeiffer / Khal-Hentz Gabriel / Jonathan LaRochelle / Kartik Subramanian / Ruili Cao / Kimberley Stegmaier / Morvarid Mohseni / Matthew J LaMarche / Michael G Acker / Peter K Sorger / Steven P Gygi / Stephen C Blacklow

eLife, Vol

2021 Volume 10

Abstract	SHP2 is a protein tyrosine phosphatase that normally potentiates intracellular signaling by growth factors, antigen receptors, and some cytokines, yet is frequently mutated in human cancer. Here, we examine the role of SHP2 in the responses of breast cancer cells to EGF by monitoring phosphoproteome dynamics when SHP2 is allosterically inhibited by SHP099. The dynamics of phosphotyrosine abundance at more than 400 tyrosine residues reveal six distinct response signatures following SHP099 treatment and washout. Remarkably, in addition to newly identified substrate sites on proteins such as occludin, ARHGAP35, and PLCγ2, another class of sites shows reduced phosphotyrosine abundance upon SHP2 inhibition. Sites of decreased phospho-abundance are enriched on proteins with two nearby phosphotyrosine residues, which can be directly protected from dephosphorylation by the paired SH2 domains of SHP2 itself. These findings highlight the distinct roles of the scaffolding and catalytic activities of SHP2 in effecting a transmembrane signaling response.
Keywords	signal transduction ; mass spectrometry ; PTPN11 ; epidermal growth factor receptor ; phosphatase ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Regulatory models of RhoA suppression by dematin, a cytoskeletal adaptor protein.

Mohseni, Morvarid / Chishti, Athar H

Cell adhesion & migration

2009 Volume 3, Issue 2, Page(s) 191–194

Abstract: Cell motility, adhesion and actin cytoskeletal rearrangements occur upon integrin-engagement to the extracellular matrix and activation of the small family of Rho GTPases, RhoA, Rac1 and Cdc42. The activity of the GTPases is regulated through ... ...

Abstract	Cell motility, adhesion and actin cytoskeletal rearrangements occur upon integrin-engagement to the extracellular matrix and activation of the small family of Rho GTPases, RhoA, Rac1 and Cdc42. The activity of the GTPases is regulated through associations with guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs) and guanine dissociation inhibitors (GDIs). Recent studies have demonstrated a critical role for actin-binding proteins, such as ezrin, radixin and moesin (ERM), in modulating the activity of small GTPases through their direct associations with GEFs, GAPs and GDI's. Dematin, an actin binding and bundling phospho-protein was first identified and characterized from the erythrocyte membrane, and has recently been implicated in regulating cell motility, adhesion and morphology by suppressing RhoA activation in mouse embryonic fibroblasts. Although the precise mechanism of RhoA suppression by dematin is unclear, several plausible and hypothetical models can be invoked. Dematin may bind and inhibit GEF activity, form an inactive complex with GDI-RhoA-GDP, or enhance GAP function. Dematin is the first actin-binding protein identified from the erythrocyte membrane that participates in GTPase signaling, and its broad expression suggests a conserved function in multiple tissues.
MeSH term(s)	Animals ; Blood Proteins/physiology ; Humans ; Microfilament Proteins ; Phosphoproteins/physiology ; rhoA GTP-Binding Protein/antagonists & inhibitors ; rhoA GTP-Binding Protein/physiology
Chemical Substances	Blood Proteins ; DMTN protein, human ; Microfilament Proteins ; Phosphoproteins ; rhoA GTP-Binding Protein (EC 3.6.5.2)
Language	English
Publishing date	2009-04-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	2268518-2
ISSN	1933-6926 ; 1933-6918
ISSN (online)	1933-6926
ISSN	1933-6918
DOI	10.4161/cam.3.2.7375
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Erythrocyte dematin is a candidate gene for Marie Unna hereditary hypotrichosis and related hairloss disorders.

Mohseni, Morvarid / Chishti, Athar H

American journal of hematology

2007 Volume 83, Issue 5, Page(s) 430–432

MeSH term(s)	Adipocytes/metabolism ; Animals ; Blood Proteins/chemistry ; Blood Proteins/deficiency ; Blood Proteins/genetics ; Blood Proteins/physiology ; Chromosome Mapping ; Chromosomes, Human, Pair 8/genetics ; Cytoskeletal Proteins ; Fibroblasts/metabolism ; Humans ; Hypotrichosis/genetics ; Mice ; Mice, Knockout ; Microfilament Proteins ; Phosphoproteins/chemistry ; Phosphoproteins/deficiency ; Phosphoproteins/genetics ; Phosphoproteins/physiology ; Protein Structure, Tertiary ; Skin/metabolism
Chemical Substances	Blood Proteins ; Cytoskeletal Proteins ; DMTN protein, human ; Dmtn protein, mouse ; Microfilament Proteins ; Phosphoproteins
Language	English
Publishing date	2007-10-05
Publishing country	United States
Document type	Letter
ZDB-ID	196767-8
ISSN	1096-8652 ; 0361-8609
ISSN (online)	1096-8652
ISSN	0361-8609
DOI	10.1002/ajh.21153
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1251: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: The headpiece domain of dematin regulates cell shape, motility, and wound healing by modulating RhoA activation.

Mohseni, Morvarid / Chishti, Athar H

Molecular and cellular biology

2008 Volume 28, Issue 15, Page(s) 4712–4718

Abstract: RhoA is known to participate in cytoskeletal remodeling events through several signaling pathways, yet the precise mechanism of its activation remains unknown. Here, we provide the first evidence that dematin functions upstream of RhoA and regulates its ... ...

Abstract	RhoA is known to participate in cytoskeletal remodeling events through several signaling pathways, yet the precise mechanism of its activation remains unknown. Here, we provide the first evidence that dematin functions upstream of RhoA and regulates its activation. Primary mouse embryonic fibroblasts were generated from a dematin headpiece domain null (HPKO) mouse, and the visualization of the actin morphology revealed a time-dependent defect in stress fiber formation, membrane protrusions, cell motility, and cell adhesion. Rescue experiments using RNA interference and transfection assays revealed that the observed phenotypes are due to a null effect and not a gain of function in the mutant fibroblasts. In vivo wounding of adult HPKO mouse skin showed a decrease in wound healing (reepithelialization and granulation) compared to the wild-type control. Biochemical analysis of the HPKO fibroblasts revealed a sustained hyperphosphorylation of focal adhesion kinase (FAK) at tyrosine 397 as well as a twofold increase in RhoA activation. Inhibition of both RhoA and FAK signaling using C3 toxin and FRNK (focal adhesion kinase nonrelated kinase), respectively, revealed that dematin acts upstream of RhoA. Together, these results unveil a new function of dematin as a negative regulator of the RhoA activation pathway with physiological implications for normal and pathogenic signaling pathways.
MeSH term(s)	Animals ; Blood Proteins/chemistry ; Blood Proteins/metabolism ; Cell Adhesion ; Cell Membrane/enzymology ; Cell Movement ; Cell Shape ; Cytoskeletal Proteins ; Enzyme Activation ; Fibroblasts/cytology ; Fibroblasts/enzymology ; Focal Adhesion Protein-Tyrosine Kinases/metabolism ; Humans ; Mice ; Mice, Inbred C57BL ; Phosphoproteins/chemistry ; Phosphoproteins/metabolism ; Protein Structure, Tertiary ; Protein Transport ; RNA, Small Interfering/metabolism ; Transfection ; Wound Healing ; rhoA GTP-Binding Protein/metabolism
Chemical Substances	Blood Proteins ; Cytoskeletal Proteins ; Dmtn protein, mouse ; Phosphoproteins ; RNA, Small Interfering ; Focal Adhesion Protein-Tyrosine Kinases (EC 2.7.10.2) ; rhoA GTP-Binding Protein (EC 3.6.5.2)
Language	English
Publishing date	2008-05-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	779397-2
ISSN	1098-5549 ; 0270-7306
ISSN (online)	1098-5549
ISSN	0270-7306
DOI	10.1128/MCB.00237-08
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1666: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito