Adhesion-related Kinase Repression of Gonadotropin-releasing Hormone Gene Expression Requires Rac Activation of the Extracellular Signal-regulated Kinase Pathway

Allen, Mary A.; Xu, Mei; Linseman, Daniel A.; Pawlowski, John E.; Bokoch, Gary M.; Heidenreich, Kim A.; Wierman, Margaret E.

doi:10.1074/jbc.m200826200

Cited by 41 publications

(39 citation statements)

References 70 publications

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“…MEF2 proteins were recently reported to regulate activitydependent synapse formation (Flavell et al, 2006;Shalizi et al, 2006), and can act synergistically with the ubiquitous transcription factor Sp1 to influence the restricted expression of a great many neuron-specific genes (Krainc et al, 1998;Okamoto et al, 2000Okamoto et al, , 2002Allen et al, 2002). These findings are consistent with the notion that MEF2 proteins regulate neuronal development not only by promoting survival but also by inducing differentiation.…”

Section: Introductionsupporting

confidence: 81%

Myocyte Enhancer Factor 2C as a Neurogenic and Antiapoptotic Transcription Factor in Murine Embryonic Stem Cells

McKercher²,

Cui³

et al. 2008

Journal of Neuroscience

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Cell-based therapies require a reliable source of cells that can be easily grown, undergo directed differentiation, and remain viable after transplantation. Here, we generated stably transformed murine ES (embryonic stem) cells that express a constitutively active form of myocyte enhancer factor 2C (MEF2CA). MEF2C has been implicated as a calcium-dependent transcription factor that enhances survival and affects synapse formation of neurons as well as differentiation of cardiomyocytes. We now report that expression of MEF2CA, both in vitro and in vivo, under regulation of the nestin enhancer effectively produces "neuronal" progenitor cells that differentiate into a virtually pure population of neurons. Histological, electrophysiological, and behavioral analyses demonstrate that MEF2C-directed neuronal progenitor cells transplanted into a mouse model of cerebral ischemia can successfully differentiate into functioning neurons and ameliorate stroke-induced behavioral deficits.

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Section: Introductionsupporting

confidence: 81%

Myocyte Enhancer Factor 2C as a Neurogenic and Antiapoptotic Transcription Factor in Murine Embryonic Stem Cells

McKercher²,

Cui³

et al. 2008

Journal of Neuroscience

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“…Ten micrograms of lysate protein for Western blotting of RAS and c-myc was separated by SDS-PAGE using a 10% polyacrylamide gel and electroblotted onto a PVDF membrane (Du Pont, Boston, MA, U.S.A.). After blockage of nonspecific binding sites for 1 h with 5% nonfat milk in PBS containing 0.1% Tween 20, the membrane was incubated overnight at 4°C with anti-human RAS antibody, clone RAS10 (Upstate, Charlottesville, VA, U.S.A.), which detects mutated RAS 10) or with anti-human c-myc antibody (Santa Cruz, Santa Cruz, CA, U.S.A.). The membranes were then washed 3 times with PBS containing 0.1% Tween 20, incubated further with HRPconjugated sheep anti-mouse or donkey anti-rabbit Ig antibody (Amersham) at room temperature, and then washed 3 times with PBS containing 0.1% Tween 20.…”

Section: Let-7 Microrna Functions As a Potential Growth Suppressor Inmentioning

confidence: 99%

let-7 MicroRNA Functions as a Potential Growth Suppressor in Human Colon Cancer Cells

Akao

Nakagawa

Naoe

2006

Biological & Pharmaceutical Bulletin

569

397

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The microRNAs (miRNAs) are an extensive class of small noncoding RNAs, 18 to 25 nucleotides in length, with the role of regulating gene expression through translational repression by base-pairing with partially complementary mRNAs.1) Currently, more than 3000 miRNAs have been annotated from a wide range of organisms including plants, worms, flies, mammals, and viruses. 2,3) The expression of miRNAs is regulated developmentally and spatially, and is involved in cell differentiation, proliferation, and death. 2)Recently several reports have indicated the involvement of miRNAs in human cancer and further that miRNAs might be used in future therapeutic and diagnostic applications.4) Especially, the expression level of let-7 miRNA was reduced in human lung cancer, 5) and it was shown to be the anticancer miRNA that represses RAS and/or c-MYC expression at the translational level.6) On the other hand, it has been established that genetic aberration of RAS and over-expression of c-myc are frequently involved in colon cancer. 7-9) Such findings led us to speculate that let-7 may also be reduced in its expression in colon cancer cells.In the current study, we focused on the expression of let-7 miRNA in colon cancer and its expression profile. Our functional analysis indicates that let-7 may function as one of the growth suppressive miRNAs in human colon cancer cells. MATERIALS AND METHODS Patients and Tissue PreparationAll human tissue samples were specimens from patients who had undergone biopsy for histological diagnosis of colon cancer at Saiseikai Ibaraki hospital, Ibaraki, Osaka, between 2000 and 2003. Informed consent in writing was obtained from each patient. The tumor and its adjacent normal tissues were also obtained. Each specimen was divided into 2 parts. One of them was subjected to Western blot analysis, and the other was used for extraction of RNA and DNA.Cell Culture and Cell Viability Human malignant cell lines SW480, DLD-1, and COLO101 (colon cancer); HL60 (myeloid leukemia); U937 (monocytic leukemia); Jurkat (Tcell leukemia); PC3 and LNCaP (prostate cancer); SH-SY5Y (neuroblastoma); HeLa (cervical cancer); and HuH7 (hepatic cancer) were grown in RPMI-1640 medium supplemented with 10% (v/v) heat-inactivated FBS (Sigma, St. Louis, MO, U.S.A.) and 2 mM L-glutamine under an atmosphere of 95% air and 5% CO 2 at 37°C. The number of viable cells was determined by the trypan-blue dye exclusion test. Plating efficiencies (the average number of colonies per 60-mm dish divided by the number of cells seeded per dish (ϫ100) were determined 14 d following inoculation of 1000 cells. The ability of the cells to grow as colonies in or on the soft agar was assessed. Briefly, 10 3 individual trypsinized cells were suspended in 5 ml RPMI 1640 medium/10% FBS/0.35% liquid Bacto-agar (Difco Laboratories. Inc.) at 40°C, immediately poured onto a 4-ml basal layer of 0.5% Bactoagar/RPMI 1640 medium/10% FBS in a 60-mm dish, and incubated at 37.5°C. The dishes were examined for the presence of colonies growing in the 0.35% agar ...

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“…Axl activation of the PI3K-Ras pathway and P38 MAPK is involved in GnRH neuronal cell migration [16,43] and hepatocyte growth factor/scatter factor-activated MET signalling is required for GnRH neuronal survival [44]. ERK and PI3K/ Akt pathways mediate Gas6/Axl signalling, which protects GnRH neurons from programmed cell death across neuronal migration [17].…”

Section: Reviewmentioning

confidence: 99%

“…TAM activates several intracellular signalling pathways, including PI3K (phosphatidylinositol-3 -kinase)-Akt, extracellular signal-regulated kinase 1/2 (ERK1/2), and/or P38 MAPK (mitogenactivated protein kinase) [16][17][18][19][20][21]. Gas6/Axl promotes cytoskeletal remodelling and the migration of GnRH neuronal cells via activation of P38 PI3K and Rho family GTPase Rac signalling.…”

Section: Introductionmentioning

confidence: 99%

“…Gas6/Axl promotes cytoskeletal remodelling and the migration of GnRH neuronal cells via activation of P38 PI3K and Rho family GTPase Rac signalling. Axl phosphorylates the p85 subunit of PI3K and contributes to Rac activation, which is required for Gas6/Axl-induced neuron migration [16,17]. Gas6/Axl/PI3K-Akt promotes the survival of oligodendrocytes in human foetal spinal cord [20].…”

Section: Introductionmentioning

confidence: 99%

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The Role of the TAM Family of Receptor Tyrosine Kinases in Neural Development and Disorders

Zhang¹,

Qi²

2018

Neuropsychiatry

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Tyrosine kinase receptor 3 (Tyro3), Axl, and Mer constitute the TAM family of receptor tyrosine kinases. These receptor tyrosine kinases are characterized by a conserved sequence within the kinase domain and adhesion molecule-like extracellular domains. The TAM family and their shared ligands, growth arrest-specific gene-6 (Gas6) and protein S, are differentially expressed in the developing and adult nervous systems. The TAM family regulates normal cellular processes and plays an important role in nervous system development and diseases, including cell proliferation/survival, cell adhesion and migration, neuronal differentiation, cell apoptosis, myelination, degeneration, and immune regulation. This review summarizes the developing expression of the TAM family and ligands and their function in neural development and nervous system diseases. Further research will be necessary to fully elucidate the function of the TAM family and to evaluate the clinical implications of TAM family expression and activation in nervous system diseases.

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Adhesion-related Kinase Repression of Gonadotropin-releasing Hormone Gene Expression Requires Rac Activation of the Extracellular Signal-regulated Kinase Pathway

Cited by 41 publications

References 70 publications

Myocyte Enhancer Factor 2C as a Neurogenic and Antiapoptotic Transcription Factor in Murine Embryonic Stem Cells

Myocyte Enhancer Factor 2C as a Neurogenic and Antiapoptotic Transcription Factor in Murine Embryonic Stem Cells

let-7 MicroRNA Functions as a Potential Growth Suppressor in Human Colon Cancer Cells

The Role of the TAM Family of Receptor Tyrosine Kinases in Neural Development and Disorders

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