Abstract 474: ERK4-deficiency Potentiates the TAC-induced Increase in Collagen1-α 1 Messenger RNA in Mice

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Joelle Trepanier ◽  
Dharmendra D Dingar ◽  
Marc-Antoine Gillis ◽  
Pramod Sahadevan ◽  
Yan Fen Shi ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Messenger Rna ◽  
Matrix Protein ◽  
Interstitial Fibrosis ◽  
Cardiac Fibroblasts ◽  
Primary Source ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Matrix Protein ◽  
Systolic And Diastolic Function

Cardiac hypertrophy, a common consequence of cardiopathologies such as hypertension and myocardial infarcts, involves formation of excessive interstitial fibrosis, which may impair cardiac function. Fibroblasts are the primary source of extracellular matrix protein. Extracellular-regulated kinase 4 (ERK4) is an atypical mitogen-activated protein kinase (MAPK). The regulation and role of ERK4 in the heart are currently unidentified and its only known target is MAP kinase-activated protein kinase 5 (MK5), a kinase involved in regulating fibroblast function. Following constriction of the transverse aorta (TAC), MK5 haplodeficient mice showed an attenuation of the TAC-induced increase in collagen 1-α 1 mRNA at 2-wk post-TAC and reduced hypertrophy 8-wk post-TAC. Further studies revealed MK5 immunoreactivity in cardiac fibroblasts but not myocytes. MK5 immunoprecipitates from whole heart contain ERK3 immunoreactivity, but not that of ERK4 or p38 MAPK. This study was to examine the role of ERK4 in myocardial structure, function, and remodeling 3-wk post-TAC. At 12 wk of age, echocardiographic imaging revealed systolic and diastolic function in male ERK4 -/- mice were similar to wild-type littermates (ERK4 +/+ ). Three weeks post-TAC, hypertrophy was similar in ERK4 +/+ and ERK4 -/- mice. Transcripts for BNP and βMHC increased to similar extent in TAC- ERK4 +/+ and TAC- ERK4 -/- mice. Two-way ANOVA indicated that ERK4 deficiency altered the effect of TAC on TGFβ 1 and collagen 1-α 1 transcript levels with each being higher in TAC-ERK4 -/- mice. Furthermore, MK5 immunoprecipitates from cardiac fibroblast lysates did not contain ERK4 immunoreactivity. Additional experiments revealed the presence of ERK4 immunoreactivity in myocytes but not fibroblasts. These results suggest 1) ERK4 may be involved in myocyte - fibroblast communication during myocardial remodeling and 2) in cardiac myocytes, ERK4 is part of a novel signaling cascade that does not involve MK5.

β1 integrins are distributed in adhesion structures with fibronectin and caveolin and in coated pits

2003 ◽  
Vol 81 (5) ◽  
pp. 335-348 ◽  
Author(s):  
Nikhat D Boyd ◽  
Bosco M. C Chan ◽  
Nils O Petersen
Keyword(s):  
Extracellular Matrix ◽  
Protein Kinase ◽  
Matrix Protein ◽  
Adaptor Protein ◽  
Cytoskeletal Proteins ◽  
Matrix Proteins ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Matrix Protein ◽  
Coated Pits ◽  
Mitogen Activated Protein

Integrins are found in adhesion structures, which link the extracelullar matrix to cytoskeletal proteins. Here, we attempt to further define the distribution of β1 integrins in the context of their association with matrix proteins and other cell surface molecules relevant to the endocytic process. We find that β1 integrins colocalize with fibronectin in fibrillar adhesion structures. A fraction of caveolin is also organized along these adhesion structures. The extracellular matrix protein laminin is not concentrated in these structures. The α4β1 integrin exhibits a distinct distribution from other β1 integrins after cells have adhered for 1 h to extracellular matrix proteins but is localized in adhesion structures after 24 h of adhesion. There are differences between the fibronectin receptors: α5β1 integrins colocalize with adaptor protein-2 in coated pits, while α4β1 integrins do not. This parallels our earlier observation that of the two laminin receptors, α1β1 and α6β1, only αaβ1 integrins colocalize with adaptor protein-2 in coated pits. Calcium chelation or inhibition of mitogen-activated protein kinase kinase, protein kinase C, or src did not affect localization of α1β1 and α5β1 integrins in coated pits. Likewise, the integrity of coated-pit structures or adhesion structures is not required for integrin and adaptor protein-2 colocalization. This suggests a robust and possibly constitutive interaction between these integrins and coated pits.Key words: adhesion, endocytosis, extracellular matrix, microscopy, confocal, signalling.

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.

Role of p38 Mitogen-Activated Protein Kinase in Thrombus Formation

2004 ◽  
Vol 24 (4) ◽  
pp. 283-296 ◽  
Author(s):  
Kanako Sakurai ◽  
Yuji Matsuo ◽  
Tatsuhiko Sudo ◽  
Yoh Takuwa ◽  
Sadao Kimura ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Thrombus Formation ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein

scholarly journals Dual-mode regulation of the APC/C by CDK1 and MAPK controls meiosis I progression and fidelity

2014 ◽  
Vol 204 (6) ◽  
pp. 891-900 ◽  
Author(s):  
Ibtissem Nabti ◽  
Petros Marangos ◽  
Jenny Bormann ◽  
Nobuaki R. Kudo ◽  
John Carroll
Keyword(s):  
Protein Kinase ◽  
Spindle Assembly Checkpoint ◽  
Mitogen Activated Protein Kinase ◽  
Cyclin Dependent Kinase ◽  
Anaphase Promoting Complex ◽  
Female Meiosis ◽  
Dual Mode ◽  
Mitogen Activated Protein ◽  
Meiosis I

Female meiosis is driven by the activities of two major kinases, cyclin-dependent kinase 1 (Cdk1) and mitogen-activated protein kinase (MAPK). To date, the role of MAPK in control of meiosis is thought to be restricted to maintaining metaphase II arrest through stabilizing Cdk1 activity. In this paper, we find that MAPK and Cdk1 play compensatory roles to suppress the anaphase-promoting complex/cyclosome (APC/C) activity early in prometaphase, thereby allowing accumulation of APC/C substrates essential for meiosis I. Furthermore, inhibition of MAPK around the onset of APC/C activity at the transition from meiosis I to meiosis II led to accelerated completion of meiosis I and an increase in aneuploidy at metaphase II. These effects appear to be mediated via a Cdk1/MAPK-dependent stabilization of the spindle assembly checkpoint, which when inhibited leads to increased APC/C activity. These findings demonstrate new roles for MAPK in the regulation of meiosis in mammalian oocytes.

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