scholarly journals Lysophosphatidic acid prevents apoptosis in fibroblasts via Gi-protein-mediated activation of mitogen-activated protein kinase

2000 ◽  
Vol 352 (1) ◽  
pp. 135-143 ◽  
Author(s):  
Xianjun FANG ◽  
Shuangxing YU ◽  
Ruth LAPUSHIN ◽  
Yiling LU ◽  
Tatsuro FURUI ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cell Survival ◽  
Lysophosphatidic Acid ◽  
Protein S ◽  
Cell Types ◽  
Mitogen Activated Protein Kinase ◽  
Proliferative Effect ◽  
Mitogen Activated Protein ◽  
Gi Protein ◽  
Induced Apoptosis

Lysophosphatidic acid (LPA) is a naturally occurring phospholipid with multiple biological functions. In the present study, we demonstrate that, besides its mitogenic activity, LPA is a potent survival factor, preventing serum-deprivation-induced apoptosis in fibroblasts and other cell types. Both the proliferative effect and survival activity of LPA are sensitive to the action of pertussis toxin (PTX), indicating that both processes are mediated by Gi protein(s). We therefore focused on the role of Gi-protein-mediated signalling events in the promotion of cell survival by LPA. In addition to activation of mitogen-activated protein kinase (MAPK), LPA stimulates a modest PTX-sensitive phosphorylation/activation of the serine/threonine kinase Akt, a survival mediator downstream of phosphoinositide 3-kinase (PI3K). Inhibition of PI3K with LY 294002 or wortmannin resulted in a marked inhibition of LPA-induced DNA synthesis, and yet the survival activity of LPA decreased by only 20–30%, suggesting a limited input of the PI3K–Akt cascade in LPA-induced cell survival. In contrast, inhibition of MAPK activation by the MEK-1 inhibitor, PD 98059, blocked both the proliferative and survival effects of LPA. These results indicate that LPA promotes cell survival largely via Gi-protein-mediated activation of ERK1/ERK2, or other PD 98059-sensitive member(s) of the MAPK family.

scholarly journals Lysophosphatidic acid prevents apoptosis in fibroblasts via Gi-protein-mediated activation of mitogen-activated protein kinase

2000 ◽  
Vol 352 (1) ◽  
pp. 135 ◽  
Author(s):  
Xianjun FANG ◽  
Shuangxing YU ◽  
Ruth LaPUSHIN ◽  
Yiling LU ◽  
Tatsuro FURUI ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Lysophosphatidic Acid ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Gi Protein

Stromal-derived factor 1 and thrombopoietin regulate distinct aspects of human megakaryopoiesis

Blood ◽  
2000 ◽  
Vol 96 (13) ◽  
pp. 4142-4151 ◽  
Author(s):  
Marcin Majka ◽  
Anna Janowska-Wieczorek ◽  
Janina Ratajczak ◽  
M. Anna Kowalska ◽  
Gaston Vilaire ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Intracellular Signaling ◽  
Phosphatidyl Inositol ◽  
Mek Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Proliferative Effect ◽  
Normal Human ◽  
And Migration ◽  
Induced Apoptosis

Abstract The role of the chemokine binding stromal-derived factor 1 (SDF-1) in normal human megakaryopoiesis at the cellular and molecular levels and its comparison with that of thrombopoietin (TPO) have not been determined. In this study it was found that SDF-1, unlike TPO, does not stimulate αIIbβ3+ cell proliferation or differentiation or have an antiapoptotic effect. However, it does induce chemotaxis, trans-Matrigel migration, and secretion of matrix metalloproteinase 9 (MMP-9) and vascular endothelial growth factor (VEGF) by these cells, and both SDF-1 and TPO increase the adhesion of αIIbβ3+ cells to fibrinogen and vitronectin. Investigating the intracellular signaling pathways induced by SDF-1 and TPO revealed some overlapping patterns of protein phosphorylation/activation (mitogen-activated protein kinase [MAPK] p42/44, MAPK p38, and AKT [protein kinase B]) and some that were distinct for TPO (eg, JAK-STAT) and for SDF-1 (eg, NF-κB). It was also found that though inhibition of phosphatidyl-inositol 3-kinase (PI-3K) by LY294002 in αIIbβ3+ cells induced apoptosis and inhibited chemotaxis adhesion and the secretion of MMP-9 and VEGF, the inhibition of MAPK p42/44 (by the MEK inhibitor U0126) had no effect on the survival, proliferation, and migration of these cells. Hence, it is suggested that the proliferative effect of TPO is more related to activation of the JAK-STAT pathway (unique to TPO), and the PI-3K–AKT axis is differentially involved in TPO- and SDF-1–dependent signaling. Accordingly, PI-3K is involved in TPO-mediated inhibition of apoptosis, TPO- and SDF-1–regulated adhesion to fibrinogen and vitronectin, and SDF-1–mediated migration. This study expands the understanding of the role of SDF-1 and TPO in normal human megakaryopoiesis and indicates the molecular basis of the observed differences in cellular responses.

scholarly journals Zamzam water protects cancer cells from chemotherapy-induced apoptosis via mitogen-activated protein kinase-dependent pathway

2019 ◽  
Vol 118 ◽  
pp. 109376
Author(s):  
Abdul Khalid Siraj ◽  
Rafia Begum ◽  
Roxanne Melosantos ◽  
Wafaa Albalawy ◽  
Jehan Abboud ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cancer Cells ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Induced Apoptosis ◽  
Dependent Pathway

scholarly journals Selective expression of the scaffold protein JSAP1 in spermatogonia and spermatocytes

Reproduction ◽  
2006 ◽  
Vol 131 (4) ◽  
pp. 711-719 ◽  
Author(s):  
Munkhuu Bayarsaikhan ◽  
Akiko Shiratsuchi ◽  
Davaakhuu Gantulga ◽  
Yoshinobu Nakanishi ◽  
Katsuji Yoshioka
Keyword(s):  
Protein Kinase ◽  
Western Blotting ◽  
Cell Types ◽  
Mapk Signaling ◽  
Scaffold Protein ◽  
Mitogen Activated Protein Kinase ◽  
Interacting Protein ◽  
Early Postnatal Development ◽  
Mitogen Activated Protein ◽  
Signaling Modules

Scaffold proteins of mitogen-activated protein kinase (MAPK) intracellular signal transduction pathways mediate the efficient and specific activation of the relevant MAPK signaling modules. Previously, our group and others have identified c-Jun NH2-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1, also known as JNK-interacting protein 3) as a scaffold protein for JNK MAPK pathways. Although JSAP1 is expressed in the testis in adults, its expression during development has not been investigated. In addition, it is unknown which types of cells in the testis express the scaffold protein. Here, we examined the expression of JSAP1 in the testis of mice aged 14 days, 20 days, 6 weeks, and 12 weeks by immunohistochemistry and Western blotting. The specificity of the anti-JSAP1 antibody was evaluated from its reactivity to exogenously expressed JSAP1 and a structurally related protein, and by antigen-absorption experiments. The immunohistochemical analyses with the specific antibody showed that the JSAP1 protein was selectively expressed in the spermatogonia and spermatocytes, but not in other cell types, including spermatids and somatic cells, during development. However, not all spermatogonia and spermatocytes were immunopositive either, especially in the 12-week-old mouse testis. Furthermore, we found by Western blotting that the expression levels of JSAP1 protein vary during development; there is high expression until 6 weeks after birth, which approximately corresponds to the end of the first wave of spermatogenesis. Collectively, these results suggest that JSAP1 function may be important in spermatogenic cells during early postnatal development.

Involvement of the mitogen-activated protein kinase pathway in soft-shelled turtle iridovirus-induced apoptosis

APOPTOSIS ◽  
2011 ◽  
Vol 16 (6) ◽  
pp. 581-593 ◽  
Author(s):  
Youhua Huang ◽  
Xiaohong Huang ◽  
Jia Cai ◽  
Fuzhou Ye ◽  
Qiwei Qin
Keyword(s):  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Induced Apoptosis ◽  
Kinase Pathway

AMPK, MAPK and Bax in the heart: some questions answered

2008 ◽  
Vol 412 (2) ◽  
pp. e15-e16 ◽  
Author(s):  
Vilmante Borutaite
Keyword(s):  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Wide Field ◽  
Biochemical Journal ◽  
Mitogen Activated Protein ◽  
Isolated Cardiac Myocytes ◽  
And Migration ◽  
Induced Apoptosis ◽  
Amp Activated Protein Kinase ◽  
Rapid Activation

The question of how Bax is activated during apoptosis to perform its role in permeabilization of mitochondrial membranes is intriguing for investigators in the wide field of cell death research. In their paper published in the Biochemical Journal in 2006, Capano and Crompton presented their discovery that simulated ischaemia causes rapid activation of AMPK (AMP-activated protein kinase) which phosphorylates and activates p38 MAPK (mitogen-activated protein kinase) leading to Bax activation and translocation to mitochondria in isolated cardiac myocytes. This was the first report on the molecular mechanism of Bax activation and migration during ischaemia-induced apoptosis in cardiomyocytes.

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