Signal Transduction and Actin in the Regulation of G1-Phase Progression

Boonstra, Johannes; Moes, Maarten J. A.

doi:10.1615/critreveukargeneexpr.v15.i3.70

Cited by 10 publications

(5 citation statements)

References 167 publications

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“…External signal molecules, such as growth factors and extracellular matrix components, act via signal transduction pathways (which include those based on MAP kinase and PI-3 kinase) to determine whether the cell in G1 phase continues proliferation or undergoes apoptosis, differentiation, or quiescence. Actin dynamics have been proposed as important in this progression through G1 given actin’s role in these pathways, in transcription (see below) and in cell shape and structure [75]. Both glutamine and glucose are needed for progression from G1 into S phase.…”

Section: Presentation Of the Hypothesismentioning

confidence: 99%

Sensor potency of the moonlighting enzyme-decorated cytoskeleton: the cytoskeleton as a metabolic sensor

et al. 2013

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BackgroundThere is extensive evidence for the interaction of metabolic enzymes with the eukaryotic cytoskeleton. The significance of these interactions is far from clear.Presentation of the hypothesisIn the cytoskeletal integrative sensor hypothesis presented here, the cytoskeleton senses and integrates the general metabolic activity of the cell. This activity depends on the binding to the cytoskeleton of enzymes and, depending on the nature of the enzyme, this binding may occur if the enzyme is either active or inactive but not both. This enzyme-binding is further proposed to stabilize microtubules and microfilaments and to alter rates of GTP and ATP hydrolysis and their levels.Testing the hypothesisEvidence consistent with the cytoskeletal integrative sensor hypothesis is presented in the case of glycolysis. Several testable predictions are made. There should be a relationship between post-translational modifications of tubulin and of actin and their interaction with metabolic enzymes. Different conditions of cytoskeletal dynamics and enzyme-cytoskeleton binding should reveal significant differences in local and perhaps global levels and ratios of ATP and GTP. The different functions of moonlighting enzymes should depend on cytoskeletal binding.Implications of the hypothesisThe physical and chemical effects arising from metabolic sensing by the cytoskeleton would have major consequences on cell shape, dynamics and cell cycle progression. The hypothesis provides a framework that helps the significance of the enzyme-decorated cytoskeleton be determined.

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Section: Presentation Of the Hypothesismentioning

confidence: 99%

Sensor potency of the moonlighting enzyme-decorated cytoskeleton: the cytoskeleton as a metabolic sensor

et al. 2013

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“…In this respect it is of interest that the actin cytoskeleton has been demonstrated to play an essential role in signal transduction (Boonstra and Moes 2005; Heng and Koh 2010). The first indications for the relationship between actin and signal transduction were obtained by studies on the effects of growth factors on cell morphology.…”

Section: Introductionmentioning

confidence: 99%

Attachment of HeLa cells during early G1 phase

Moes

Bijvelt

Boonstra

2011

Histochem Cell Biol

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Both growth factor directed and integrin dependent signal transduction were shown to take place directly after completion of mitosis. The local activation of these signal transduction cascades was investigated in early G1 cells. Interestingly, various key signal transduction proteins were found in blebs at the cell membrane within 30 min after mitosis. These membrane blebs appeared in round, mitotic-like cells and disappeared rapidly during spreading of the cells in G1 phase. In addition to tyrosine-phosphorylated proteins, the blebs contained also phosphorylated FAK and phosphorylated MAP kinase. The formation of membrane blebs in round, mitotic cells before cell spreading is not specific for mitotic cells, because similar features were observed in trypsinized cells. Just before cell spreading also these cells exhibited membrane blebs containing active signal transduction proteins. Inhibition of signal transduction did not affect membrane bleb formation, suggesting that the membrane blebs were formed independent of signal transduction.

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“…Actin plays an essential role in a wide variety of dynamic events in mammalian cells, amongst them cell motility, cytokinesis, and cell–cell and cell–matrix interactions [1–4]. Actin dynamics are determined by the activities of a large number of actin-binding proteins.…”

Section: Introductionmentioning

confidence: 99%

Novel role of cPLA2α in membrane and actin dynamics

Moes

Boonstra

Regan-Klapisz

2010

Cell. Mol. Life Sci.

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Actin-directed processes such as membrane ruffling and cell migration are regulated by specific signal transduction pathways that become activated by growth factor receptors. The same signaling pathways that lead to modifications in actin dynamics also activate cPLA 2 a. Moreover, arachidonic acid, the product of cPLA 2 a activity, is involved in regulation of actin dynamics. Therefore, it was investigated whether cPLA 2 a plays a role in actin dynamics, more specifically during growth factor-induced membrane ruffling and cell migration. Upon stimulation of ruffling and cell migration by growth factors, endogenous cPLA 2 a and its active phosphorylated form were shown to relocate at protrusions of the cell membrane involved in actin and membrane dynamics. Inhibition of cPLA 2 a activity with specific inhibitors blocked growth factorinduced membrane and actin dynamics, suggesting an important role for cPLA 2 a in these processes.

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Signal Transduction and Actin in the Regulation of G1-Phase Progression

Cited by 10 publications

References 167 publications

Sensor potency of the moonlighting enzyme-decorated cytoskeleton: the cytoskeleton as a metabolic sensor

Sensor potency of the moonlighting enzyme-decorated cytoskeleton: the cytoskeleton as a metabolic sensor

Attachment of HeLa cells during early G1 phase

Novel role of cPLA2α in membrane and actin dynamics

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