Hepatocyte Growth Factor-induced Asef-IQGAP1 Complex Controls Cytoskeletal Remodeling and Endothelial Barrier

Tian, Yufeng; Gawlak, Grzegorz; Shah, Alok S.; Higginbotham, Katherine; Tian, Xinxin; Kawasaki, Yuki; Akiyama, Tetsu; Sacks, David B.; Birukova, Anna A.

doi:10.1074/jbc.m114.620377

Cited by 38 publications

(34 citation statements)

References 54 publications

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“…89). IQGAP1 is able to bind to ARP3 (actin-related protein 3) and cortactin, thereby linking RAC1 effectors responsible for cortical actin polymerization with ASEF and active RAC1.…”

Section: Wave Regulatory Complexmentioning

confidence: 93%

“…IQGAP1 is able to bind to ARP3 (actin-related protein 3) and cortactin, thereby linking RAC1 effectors responsible for cortical actin polymerization with ASEF and active RAC1. This leads to the remodelling of peripheral actin filaments in endothelial cells 89 . Another example is the RAC GEF P-REX1, which brings RAC1 together with its target FLI1 (friend leukaemia integration 1 transcription factor) to stimulate cell migration 90 .…”

Section: Wave Regulatory Complexmentioning

confidence: 99%

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Regulating Rho GTPases and their regulators

Hodge

Ridley²

2016

Nat Rev Mol Cell Biol

734

657

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Rho GTPases regulate cytoskeletal and cell adhesion dynamics and thereby coordinate a wide range of cellular processes, including cell migration, cell polarity and cell cycle progression. Most Rho GTPases cycle between a GTP-bound active conformation and a GDP-bound inactive conformation to regulate their ability to activate effector proteins and to elicit cellular responses. However, it has become apparent that Rho GTPases are regulated by post-translational modifications and the formation of specific protein complexes, in addition to GTP-GDP cycling. The canonical regulators of Rho GTPases - guanine nucleotide exchange factors, GTPase-activating proteins and guanine nucleotide dissociation inhibitors - are regulated similarly, creating a complex network of interactions to determine the precise spatiotemporal activation of Rho GTPases.

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“…89). IQGAP1 is able to bind to ARP3 (actin-related protein 3) and cortactin, thereby linking RAC1 effectors responsible for cortical actin polymerization with ASEF and active RAC1.…”

Section: Wave Regulatory Complexmentioning

confidence: 93%

Section: Wave Regulatory Complexmentioning

confidence: 99%

Regulating Rho GTPases and their regulators

Hodge

Ridley²

2016

Nat Rev Mol Cell Biol

734

657

View full text Add to dashboard Cite

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“…Given the abundance of binding sites on the pulmonary endothelium, AM also holds promise as a lung endothelial imaging tool using 99mTechnetium labelling 117. Finally, hepatocyte growth factor has recently been shown to suppress LPS-induced endothelial activation and barrier disruption possibly via a guanine nucleotide exchange factor 118 119…”

Section: Candidate Therapies To Enhance Endothelial Barrier Functionmentioning

confidence: 99%

The pulmonary endothelium in acute respiratory distress syndrome: insights and therapeutic opportunities

Millar

Summers

Griffiths

et al. 2016

Thorax

189

181

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The pulmonary endothelium is a dynamic, metabolically active layer of squamous endothelial cells ideally placed to mediate key processes involved in lung homoeostasis. Many of these are disrupted in acute respiratory distress syndrome (ARDS), a syndrome with appreciable mortality and no effective pharmacotherapy. In this review, we consider the role of the pulmonary endothelium as a key modulator and orchestrator of ARDS, highlighting advances in our understanding of endothelial pathobiology and their implications for the development of endothelial-targeted therapeutics including cell-based therapies. We also discuss mechanisms to facilitate the translation of preclinical data into effective therapies including the application of biomarkers to phenotype patients with ARDS with a predominance of endothelial injury and emerging biotechnologies that could enhance delivery, discovery and testing of lung endothelial-specific therapeutics.

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“…Asef was essential for HGF-induced Rac activation and its association with IQGAP1. Furthermore, the translocation of IQGAP1 at the cell cortical area and its interaction with cytoskeletal regulators coractin and Arp3 was also dependent on Asef 45. The nucleotide exchange activity of Asef was necessary for its interaction with IQGAP1 and to form a protein complex at the cell periphery.…”

Section: Asef a Novel Mt-associated Rac Activator In Endothelial Barmentioning

confidence: 98%

Microtubules-Associated Rac Regulation of Endothelial Barrier: A Role of Asef in Acute Lung Injury

Karki

Birukova

2017

Journal of Investigative Medicine

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The endothelial barrier function regulated by the cytoskeletal reorganizations has been implicated in the pathogenesis of multiple lung diseases including asthma, sepsis, edema, and acute respiratory distress syndrome. The extensive studies have established that activation of small GTPase Rac is a key mechanism in endothelial barrier protection but the role of microtubules-associated Rac in the endothelial functions remains poorly understood. With the emerging evidences that microtubules disassembly also plays a critical role in actin cytoskeleton remodeling leading to endothelial permeability, the knowledge on microtubules-mediated regulation of endothelial barrier is imperative to better understand the etiology of lung injuries as well as to develop novel therapeutics against these disorders. In this regard, our recent studies have revealed some novel aspects of microtubules-mediated regulation of endothelial barrier functions and unraveled a putative role of Rac-specific guanine nucleotide exchange factor Asef in mediating the barrier protective effects of hepatocyte growth factor. In this review, we will discuss the role of this novel Rac activator Asef in endothelial barrier protection and its regulation by microtubules.

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Hepatocyte Growth Factor-induced Asef-IQGAP1 Complex Controls Cytoskeletal Remodeling and Endothelial Barrier

Cited by 38 publications

References 54 publications

Regulating Rho GTPases and their regulators

Regulating Rho GTPases and their regulators

The pulmonary endothelium in acute respiratory distress syndrome: insights and therapeutic opportunities

Microtubules-Associated Rac Regulation of Endothelial Barrier: A Role of Asef in Acute Lung Injury

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