Src-dependent phosphorylation of ROCK participates in regulation of focal adhesion dynamics

Lee, Hsiao-Hui; Tien, Sui Chih; Jou, Tzuu-Shuh; Chang, Yuan Chen; Jhong, Jheng Guang; Chang, Zee Fen

doi:10.1242/jcs.071555

Cited by 62 publications

(55 citation statements)

References 55 publications

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“…RHO signaling (spots 613 and 850), which is connected to SRC signaling also was activated (35). This activation most likely occurs via focal adhesion kinase (FAK) (spot 340) and protein kinase C (PKC) (spot 170) (36,37).…”

Section: K Pneumoniae Pneumonia Kinome Profilementioning

confidence: 99%

Kinase Activity Profiling of Gram-Negative Pneumonia

Hoogendijk

Diks

Peppelenbosch

et al. 2011

Mol Med

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Pneumonia is a severe disease with high morbidity and mortality. A major causative pathogen is the Gram-negative bacterium Klebsiella (K.) pneumoniae. Kinases play an integral role in the transduction of intracellular signaling cascades and regulate a diverse array of biological processes essential to immune cells. The current study explored signal transduction events during murine Gram-negative pneumonia using a systems biology approach. Kinase activity arrays enable the analysis of 1,024 consensus sequences of protein kinase substrates. Using a kinase activity array on whole lung lysates, cellular kinase activities were determined in a mouse model of K. pneumoniae pneumonia. Notable kinase activities also were validated with phospho-specific Western blots. On the basis of the profiling data, mitogen-activated protein kinase (MAPK) signaling via p42 mitogen-activated protein kinase (p42) and p38 mitogen-activated protein kinase (p38) and transforming growth factor β (TGFβ) activity were reduced during infection, whereas v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) (SRC) activity generally was enhanced. AKT signaling was represented in both metabolic and inflammatory (mitogen-activated protein kinase kinase 2 [MKK], apoptosis signal-regulating kinase/mitogen-activated protein kinase kinase kinase 5 [ASK] and v-raf murine sarcoma viral oncogene homolog B1 [b-RAF]) context. This study reaffirms the importance of classic inflammation pathways, such as MAPK and TGFβ signaling and reveals less known involvement of glycogen synthase kinase 3β (GSK-3β), AKT and SRC signaling cassettes in pneumonia.

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Section: K Pneumoniae Pneumonia Kinome Profilementioning

confidence: 99%

Kinase Activity Profiling of Gram-Negative Pneumonia

Hoogendijk

Diks

Peppelenbosch

et al. 2011

Mol Med

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“…To facilitate podosome rosette formation, Rho and/or ROCK II are often found to be repressed in cells. For example, active Src represses the Rho-ROCK pathway by activating RhoGAP (Arthur et al, 2000;Roof et al, 2000) or directly phosphorylating and inhibiting ROCK II (Lee et al, 2010;Pan et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Phosphorylation of moesin by c-Jun N-terminal kinase is important for podosome rosette formation in Src-transformed fibroblasts

Pan

Tseng

Chang

et al. 2013

Journal of Cell Science

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SummaryPodosomes are actin-based membrane protrusions that facilitate extracellular matrix degradation and motility of invasive cells. Podosomes can self-organize into large rosette-like structures in Src-transformed fibroblasts, osteoclasts and some highly invasive cancer cells. However, the mechanism of this assembly remains obscure. In this study, we show that the suppression of Jun N-terminal kinase (JNK) by the JNK inhibitor SP600125 or short-hairpin RNA inhibited podosome rosette formation in SrcY527F-transformed NIH3T3 fibroblasts. In addition, SrcY527F was less able to induce podosome rosettes in JNK1-null or JNK2-null mouse embryo fibroblasts than in wild-type counterparts. The kinase activity of JNK was essential for promoting podosome rosette formation but not for its localization to podosome rosettes. Moesin, a member of the ERM (ezrin, radixin and moesin) protein family, was identified as a substrate of JNK. We show that the phosphorylation of moesin at Thr558 by JNK was important for podosome rosette formation in SrcY527F-transformed NIH3T3 fibroblasts. Taken together, our results unveil a novel role of JNK in podosome rosette formation through the phosphorylation of moesin.

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“…These opposing effects of actomyosin on the turnover dynamics of focal adhesions potentially influence cell migration. Because there is a large variation in the reported lifetime of focal adhesions (Lee et al, 2010;Meenderink et al, 2010;Stricker et al, 2013), we speculate that the maturation and disassembly of focal adhesions might be modulated and coordinated by actomyosin contraction in a manner that differs between different cell types and/or under different conditions. In line with this idea, we found that treatment with a higher concentration (10 or 20 mM) of Y-27632 increased the cell migration rate (supplementary material Fig.…”

Section: Roles Of Actomyosin Contraction In Adhesion Dynamics and Celmentioning

confidence: 97%

Displacement of p130Cas from focal adhesions links actomyosin contraction to cell migration

et al. 2014

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BSTRACTCell adhesion complexes provide platforms where cell-generated forces are transmitted to the extracellular matrix (ECM). Tyrosine phosphorylation of focal adhesion proteins is crucial for cells to communicate with the extracellular environment. However, the mechanisms that transmit actin cytoskeletal motion to the extracellular environment to drive cell migration are poorly understood. We find that the movement of p130Cas (Cas, also known as BCAR1), a mechanosensor at focal adhesions, correlates with actin retrograde flow and depends upon actomyosin contraction and phosphorylation of the Cas substrate domain (CasSD). This indicates that CasSD phosphorylation underpins the physical link between Cas and the actin cytoskeleton. Fluorescence recovery after photobleaching (FRAP) experiments reveal that CasSD phosphorylation, as opposed to the association of Cas with Src, facilitates Cas displacement from adhesion complexes in migrating cells. Furthermore, the stabilization of Src-Cas binding and inhibition of myosin II, both of which sustain CasSD phosphorylation but mitigate Cas displacement from adhesion sites, retard cell migration. These results indicate that Cas promotes cell migration by linking actomyosin contractions to the adhesion complexes through a dynamic interaction with Src as well as through the phosphorylation-dependent association with the actin cytoskeleton.

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Src-dependent phosphorylation of ROCK participates in regulation of focal adhesion dynamics

Cited by 62 publications

References 55 publications

Kinase Activity Profiling of Gram-Negative Pneumonia

Kinase Activity Profiling of Gram-Negative Pneumonia

Phosphorylation of moesin by c-Jun N-terminal kinase is important for podosome rosette formation in Src-transformed fibroblasts

Displacement of p130Cas from focal adhesions links actomyosin contraction to cell migration

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