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Journal ArticleDOI

Inhibition of myosin light chain kinase by p21-activated kinase.

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TLDR
MLCK activity and MLC phosphorylation were decreased, and cell spreading was inhibited in baby hamster kidney-21 and HeLa cells expressing constitutively active PAK1, indicating that MLCK is a target for p21-activated kinases and that PAKs may regulate cytoskeletal dynamics by decreasing M LCK activity.
Abstract
p21-activated kinases (PAKs) are implicated in the cytoskeletal changes induced by the Rho family of guanosine triphosphatases Cytoskeletal dynamics are primarily modulated by interactions of actin and myosin II that are regulated by myosin light chain kinase (MLCK)-mediated phosphorylation of the regulatory myosin light chain (MLC) p21-activated kinase 1 (PAK1) phosphorylates MLCK, resulting in decreased MLCK activity MLCK activity and MLC phosphorylation were decreased, and cell spreading was inhibited in baby hamster kidney-21 and HeLa cells expressing constitutively active PAK1 These data indicate that MLCK is a target for PAKs and that PAKs may regulate cytoskeletal dynamics by decreasing MLCK activity and MLC phosphorylation

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Epithelial–mesenchymal transitions in tumour progression

TL;DR: Epithelial–mesenchymal transition provides a new basis for understanding the progression of carcinoma towards dedifferentiated and more malignant states.
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Rho GTPases and their effector proteins.

TL;DR: The main focus of this review will be Rho, Rac and Cdc42, the three best characterized mammalian Rho GTPases, though the genetic analysis of RhoGTPases in lower eukaryotes is making increasingly important contributions to this field.
Journal ArticleDOI

Ca2+ Sensitivity of Smooth Muscle and Nonmuscle Myosin II: Modulated by G Proteins, Kinases, and Myosin Phosphatase

TL;DR: It is suggested that the RhoA/ROK pathway is constitutively active in a number of organs under physiological conditions; its aberrations play major roles in several disease states, particularly impacting on Ca2+ sensitization of smooth muscle in hypertension and possibly asthma and on cancer neoangiogenesis and cancer progression.
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ROCKs: multifunctional kinases in cell behaviour

TL;DR: Recent experiments have defined new functions of ROCKs in cells, including centrosome positioning and cell-size regulation, which might contribute to various physiological and pathological states.
Journal ArticleDOI

Rho and Rac Take Center Stage

TL;DR: This work will describe how the activity of Rho proteins is regulated downstream from growth factor receptors and cell adhesion molecules by guanine nucleotide exchange factors and GTPase activating proteins.
References
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Journal ArticleDOI

Rho GTPases and the Actin Cytoskeleton

TL;DR: Members of the Rho family of small guanosine triphosphatases have emerged as key regulators of the actin cytoskeleton, and through their interaction with multiple target proteins, they ensure coordinated control of other cellular activities such as gene transcription and adhesion.
Journal ArticleDOI

Rho, Rac, and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia

TL;DR: It is reported here that cdc42, another member of the rho family, triggers the formation of a third type of actin-based structure found at the cell periphery, filopodia, in addition to stress fibers, and rho controls the assembly of focal adhesion complexes.
Journal ArticleDOI

Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase)

TL;DR: Rho appears to inhibit myosin phosphatase through the action of Rho-kinase, which is activated by GTP·RhoA, phosphorylation of MBS and MLC in NIH 3T3 cells.
Journal ArticleDOI

Focal adhesions, contractility, and signaling

TL;DR: Focal adhesions are sites of tight adhesion to the underlying extracellular matrix developed by cells in culture and are regions of signal transduction that relate to growth control.
Journal ArticleDOI

Signal transduction and regulation in smooth muscle

TL;DR: Abnormalities of these regulatory mechanisms and isoform variations may contribute to diseases of smooth muscle, and the G-protein-coupled inhibition of protein phosphatase is also likely to be impor-tant in regulating non-muscle cell functions mediated by cytoplasmic myosin II.
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