Cell shape-mediated growth control of lens epithelial cells grown in culture

Iwig, M; Glaesser, D; Bethge, Marianne

doi:10.1016/0014-4827(81)90404-3

Cited by 37 publications

(16 citation statements)

References 32 publications

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“…Overall, our results indicate that Rho kinase-dependent stress fiber formation is required for sustained activation of the MEK/ERK pathway and the mid-G 1 phase induction of cyclin D1, but not for other aspects of cdk4 or cdk2 activation. They also emphasize that G 1 phase cell cycle progression in fibroblasts does not require stress fibers if Rac/Cdc42 signaling is allowed to induce cyclin D1.Much like cells deprived of growth factors or attachment to an extracellular matrix (ECM), fibroblasts cultured under conditions that preclude cell spreading become arrested in G 1 phase of the cell cycle (14,21,26,33,36). The cyclin-dependent kinases (cdk's), cyclin D-cdk4 (or cdk6) and cyclin Ecdk2, are the key regulators of cell cycle progression through G 1 phase, and several studies now indicate that disruption of cell spreading prevents the activation of these enzymes.…”

mentioning

confidence: 99%

“…Much like cells deprived of growth factors or attachment to an extracellular matrix (ECM), fibroblasts cultured under conditions that preclude cell spreading become arrested in G 1 phase of the cell cycle (14,21,26,33,36). The cyclin-dependent kinases (cdk's), cyclin D-cdk4 (or cdk6) and cyclin Ecdk2, are the key regulators of cell cycle progression through G 1 phase, and several studies now indicate that disruption of cell spreading prevents the activation of these enzymes.…”

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confidence: 99%

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Effects of Rho Kinase and Actin Stress Fibers on Sustained Extracellular Signal-Regulated Kinase Activity and Activation of G₁ Phase Cyclin-Dependent Kinases

Roovers

Assoian

2003

Molecular and Cellular Biology

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We recently reported that Rho kinase is required for sustained ERK signaling and the consequent mid-G 1 phase induction of cyclin D1 in fibroblasts. The results presented here indicate that these Rho kinase effects are mediated by the formation of stress fibers and the consequent clustering of ␣5␤1 integrin. Mechanistically, ␣5␤1 signaling and stress fiber formation allowed for the sustained activation of MEK, and this effect was mediated upstream of Ras-GTP loading. Interestingly, disruption of stress fibers with ML-7 led to G 1 phase arrest while comparable disruption of stress fibers with Y27632 (an inhibitor of Rho kinase) or dominantnegative Rho kinase led to a more rapid progression through G 1 phase. Inhibition of either MLCK or Rho kinase blocked sustained ERK signaling, but only Rho kinase inhibition allowed for the induction of cyclin D1 and activation of cdk4 via Rac/Cdc42. The levels of cyclin E, cdk2, and their major inhibitors, p21 cip1 and p27 kip1 , were not affected by inhibition of MLCK or Rho kinase. Overall, our results indicate that Rho kinase-dependent stress fiber formation is required for sustained activation of the MEK/ERK pathway and the mid-G 1 phase induction of cyclin D1, but not for other aspects of cdk4 or cdk2 activation. They also emphasize that G 1 phase cell cycle progression in fibroblasts does not require stress fibers if Rac/Cdc42 signaling is allowed to induce cyclin D1.Much like cells deprived of growth factors or attachment to an extracellular matrix (ECM), fibroblasts cultured under conditions that preclude cell spreading become arrested in G 1 phase of the cell cycle (14,21,26,33,36). The cyclin-dependent kinases (cdk's), cyclin D-cdk4 (or cdk6) and cyclin Ecdk2, are the key regulators of cell cycle progression through G 1 phase, and several studies now indicate that disruption of cell spreading prevents the activation of these enzymes. Pharmacological inhibitors of actin polymerization block the induction of cyclin D1 (typically the rate-limiting step in formation of active cyclin D1-cdk4 or -cdk6 complexes), the downregulation of p21 cip1 and p27 kip1 (inhibitors of cyclin E-cdk2), phosphorylation of the retinoblastoma protein, and entry into S phase (10,11,22,31,32). In endothelial cells, spreading is associated with the translation of cyclin D1 mRNA, the downregulation of p27 kip1 , and S phase entry (31, 44). Similarly, when fibroblasts are cultured within collagen gels, the disruption of isometric tension leads to loss of actin stress fibers, the inactivation of extracellular signal-regulated kinases (ERKs), the loss of cyclin D1, the upregulation of p27 kip1 , and G 1 phase cell cycle arrest (22, 62). Conversely, mechanical tension stimulates focal adhesion kinase (FAK) phosphorylation (69, 81), which can induce cyclin D1 and downregulate p21 cip1 (84). These kinds of data have lent support to the idea that cell shape-dependent G 1 phase cell cycle progression is mediated, at least in part, by stress fibers and the generation of isometric tension. However, cultur...

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confidence: 99%

mentioning

confidence: 99%

Effects of Rho Kinase and Actin Stress Fibers on Sustained Extracellular Signal-Regulated Kinase Activity and Activation of G₁ Phase Cyclin-Dependent Kinases

Roovers

Assoian

2003

Molecular and Cellular Biology

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“…The first kind results from an inherent tonus in the cytoskeleton of epithelial cells in a confluent sheet (32)(33)(34). The tight junction conformations that we recognize as typical in mammary cells are compatible with this tonus in high-density cultures.…”

Section: Discussionmentioning

confidence: 63%

Mechanical tension induces lateral movement of intramembrane components of the tight junction: studies on mouse mammary cells in culture.

Pitelka¹,

Taggart²

1983

The Journal of Cell Biology

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Occluding junctions of mammary epithelial cells in nonproliferating primary culture occasionally display an atypical pattern of intramembrane strands oriented predominantly perpendicular, instead of roughly parallel, to the apical border of the junction. To test whether the orienting influence was a centripetal cytoskeletal tension often observed in epithelial sheets on fixed substrates, we seeded cells at low density; this allows them to spread maximally while forming a barely confluent pavement. The result was a fourfold increase in the percentage of junctions with the strongly aligned, atypical pattern. Closely similar configurations were observed as the earliest detectable effect of chelation of extracellular Ca ++, which induced pronounced centripetal contraction of the cell body. Externally imposed tension, applied so as to stretch cells in one direction only, affected the positions of strands in stretched junctions as might be predicted, by flattening their undulations, increasing their alignment parallel to the apical border. Thus mechanical tension alone, whether inherent in the cytoskeleton or imposed on the cell surface by exogenous force, can cause coordinate lateral displacement of macromolecular assemblies within the membranes of both joined cells.

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“…Nach einer Kulturzeit von 24 h erfolgte eine Pulsmarkierung mit 3 H-TdR (37 kBq/ml) über 4 h. Nach Abschluss der Markierungsperiode wurde der weitere Einbau des Radionuklids durch Zugabe von kaltem TdR (1 mmol/l) gestoppt. Die weitere Aufarbeitung der Proben bis zur Bestimmung des Markierungsindex erfolgte wie unter Iwig et al [12] beschrieben.…”

Section: Autoradiographisches Verfahren Zur Ermittlung Der Adhäsionsaunclassified

Humane Linsenzellen in der Kultur12 - II. Charakterisierung von etablierten Linsenzelllinien und Testung auf Eignung für Zytotoxizitätsuntersuchungen -

Iwig¹,

Glässer²,

Struck³

2001

Klin Monatsbl Augenheilkd

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Cell shape-mediated growth control of lens epithelial cells grown in culture

Cited by 37 publications

References 32 publications

Effects of Rho Kinase and Actin Stress Fibers on Sustained Extracellular Signal-Regulated Kinase Activity and Activation of G₁ Phase Cyclin-Dependent Kinases

Effects of Rho Kinase and Actin Stress Fibers on Sustained Extracellular Signal-Regulated Kinase Activity and Activation of G₁ Phase Cyclin-Dependent Kinases

Mechanical tension induces lateral movement of intramembrane components of the tight junction: studies on mouse mammary cells in culture.

Humane Linsenzellen in der Kultur12 - II. Charakterisierung von etablierten Linsenzelllinien und Testung auf Eignung für Zytotoxizitätsuntersuchungen -

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Cell shape-mediated growth control of lens epithelial cells grown in culture

Cited by 37 publications

References 32 publications

Effects of Rho Kinase and Actin Stress Fibers on Sustained Extracellular Signal-Regulated Kinase Activity and Activation of G1 Phase Cyclin-Dependent Kinases

Effects of Rho Kinase and Actin Stress Fibers on Sustained Extracellular Signal-Regulated Kinase Activity and Activation of G1 Phase Cyclin-Dependent Kinases

Mechanical tension induces lateral movement of intramembrane components of the tight junction: studies on mouse mammary cells in culture.

Humane Linsenzellen in der Kultur12 - II. Charakterisierung von etablierten Linsenzelllinien und Testung auf Eignung für Zytotoxizitätsuntersuchungen -

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Effects of Rho Kinase and Actin Stress Fibers on Sustained Extracellular Signal-Regulated Kinase Activity and Activation of G₁ Phase Cyclin-Dependent Kinases

Effects of Rho Kinase and Actin Stress Fibers on Sustained Extracellular Signal-Regulated Kinase Activity and Activation of G₁ Phase Cyclin-Dependent Kinases