Lysophosphatidic acid stimulates CREB through mitogen- and stress-activated protein kinase-1

Lee, Chang-Wook; Nam, Ju-Suk; Park, Yoon-Kyung; Choi, Ho-Kyew; Lee, Joohyun; Kim, Nam-Ho; Cho, Jae-Young; Song, Dong‐Keun; Suh, Hwal; Lee, Jong-Ho; Kim, Yung‐Hi; Huh, Sung‐Oh

doi:10.1016/s0006-291x(03)00790-3

Cited by 32 publications

(36 citation statements)

References 35 publications

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“…Our laboratory has demonstrated that LPA stimulates CREB through MSK-1 in fibroblasts (Lee et al, 2003). In the present study, LPA-stimulated CREB phosphorylation was inhibited when either ERK1/2 pathway or p38 MAPK inhibitors were tested.…”

Section: Discussionmentioning

confidence: 48%

Involvement of the cAMP Response Element Binding Protein, CREB, and Cyclin D1 in LPA-Induced Proliferation of P19 Embryonic Carcinoma Cells

Kim

Sun

Yang

et al. 2012

Molecules and Cells

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Lysophosphatidic acid (LPA) is a lipid growth factor that induces proliferation of fibroblasts by activating the cAMP response element binding protein (CREB). Here, we further investigated whether LPA induces proliferation of P19 cells, a line of pluripotent embryonic carcinoma cells. 5′-Bromo-2-deoxyuridine incorporation and cell viability assays showed that LPA stimulated proliferation of P19 cells. Immunoblot experiments with P19 cells revealed that the mitogen activated protein kinases, including p-ERK, p38, pAKT, glycogen synthase kinase 3β, and CREB were phosphorylated by treatment with 10 μM LPA. LPA-induced phosphorylation of CREB was efficiently blocked by U0126 and H89, inhibitors of the MAP kinases ERK1/2 and mitogen-and stress-activated protein kinase 1, respectively. Involvement of cyclin D1 in LPA-induced P19 cell proliferation was verified by immunoblot analysis in combination with pharmacological inhibitor treatment. Furthermore, LPA up-regulated CRE-harboring cyclin D1 promoter activity, suggesting that CREB and cyclin D1 play significant roles in LPA-induced proliferation of P19 embryonic carcinoma cells.

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Section: Discussionmentioning

confidence: 48%

Involvement of the cAMP Response Element Binding Protein, CREB, and Cyclin D1 in LPA-Induced Proliferation of P19 Embryonic Carcinoma Cells

Kim

Sun

Yang

et al. 2012

Molecules and Cells

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“…Upon their discovery, MSK1/2 were shown to phosphorylate CREB on Ser133 in vitro with a K m value much lower than those of PKA, RSK2, and MK2 (83,268), raising the possibility that MSK1 rather than RSK2 mediates the mitogen-stimulated phosphorylation of CREB. Since then, work from several groups using different pathway inhibitors has supported the involvement of MSK1/2 in CREB phosphorylation (141,207). The most convincing evidence for MSK-dependent phosphorylation of CREB comes from knockout mice.…”

Section: Mskmentioning

confidence: 99%

Activation and Function of the MAPKs and Their Substrates, the MAPK-Activated Protein Kinases

Cargnello

Roux

2011

Microbiol Mol Biol Rev

2,519

1,619

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SUMMARY The mitogen-activated protein kinases (MAPKs) regulate diverse cellular programs by relaying extracellular signals to intracellular responses. In mammals, there are more than a dozen MAPK enzymes that coordinately regulate cell proliferation, differentiation, motility, and survival. The best known are the conventional MAPKs, which include the extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Jun amino-terminal kinases 1 to 3 (JNK1 to -3), p38 (α, β, γ, and δ), and ERK5 families. There are additional, atypical MAPK enzymes, including ERK3/4, ERK7/8, and Nemo-like kinase (NLK), which have distinct regulation and functions. Together, the MAPKs regulate a large number of substrates, including members of a family of protein Ser/Thr kinases termed MAPK-activated protein kinases (MAPKAPKs). The MAPKAPKs are related enzymes that respond to extracellular stimulation through direct MAPK-dependent activation loop phosphorylation and kinase activation. There are five MAPKAPK subfamilies: the p90 ribosomal S6 kinase (RSK), the mitogen- and stress-activated kinase (MSK), the MAPK-interacting kinase (MNK), the MAPK-activated protein kinase 2/3 (MK2/3), and MK5 (also known as p38-regulated/activated protein kinase [PRAK]). These enzymes have diverse biological functions, including regulation of nucleosome and gene expression, mRNA stability and translation, and cell proliferation and survival. Here we review the mechanisms of MAPKAPK activation by the different MAPKs and discuss their physiological roles based on established substrates and recent discoveries.

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“…5A) deposition in myocilin-transfected cells was restored by treatment with LPA. Although capable of activating multiple signaling pathways, including pathways involving phospholipase C and mitogen-activated protein kinase (37), LPA has been shown to particularly stimulate Rhodependent pathways (38,39).…”

Section: Discussionmentioning

confidence: 99%

Rho GTPase and cAMP/Protein Kinase A Signaling Mediates Myocilin-induced Alterations in Cultured Human Trabecular Meshwork Cells

Shen

Koga

Park

et al. 2008

Journal of Biological Chemistry

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Myocilin is a gene linked to the most common form of glaucoma, a major blinding disease. The trabecular meshwork (TM), a specialized eye tissue, is believed to be involved, at least in part, in the development of glaucoma. The myocilin expression is known to be up-regulated by glucocorticoids in TM cells, and an altered myocilin level may be the culprit in conditions such as corticosteroid glaucoma. Wild type myocilin, when transfected into cultured human TM cells, induced a dramatic loss of actin stress fibers and focal adhesions. Myocilin transfectants displayed a heightened sensitivity to trypsin. Adhesion to fibronectin, collagens, and vitronectin was compromised. The fibronectin deposition and the levels of fibronectin protein and mRNA were also reduced in myocilin transfectants. The fibronectin deposition could be restored by treatment with lysophosphatidic acid, a Rho stimulator. Assays further revealed that upon myocilin overexpression, the activity of RhoA was diminished, whereas the cAMP level and the protein kinase A (PKA) activity were augmented. Myocilin protein did not affect actin polymerization. The collapse of actin stress fibers and increased trypsin sensitivity from myocilin transfection could be reverted by coexpression of constitutively active RhoA or by treatment with PKA inhibitor H-89. The PKA activity, however, was not modified by co-expression of either constitutively active or dominant negative RhoA. These results demonstrate that myocilin has a deadhesive activity and triggers signaling events. cAMP/PKA activation and the downstream Rho inhibition are possible mechanisms by which myocilin in overabundance may lead to TM cell or tissue damage.

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Lysophosphatidic acid stimulates CREB through mitogen- and stress-activated protein kinase-1

Cited by 32 publications

References 35 publications

Involvement of the cAMP Response Element Binding Protein, CREB, and Cyclin D1 in LPA-Induced Proliferation of P19 Embryonic Carcinoma Cells

Involvement of the cAMP Response Element Binding Protein, CREB, and Cyclin D1 in LPA-Induced Proliferation of P19 Embryonic Carcinoma Cells

Activation and Function of the MAPKs and Their Substrates, the MAPK-Activated Protein Kinases

Rho GTPase and cAMP/Protein Kinase A Signaling Mediates Myocilin-induced Alterations in Cultured Human Trabecular Meshwork Cells

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