scholarly journals Neuronal Wiskott‐Aldrich syndrome protein regulates TGF‐β1‐mediated lung vascular permeability

2016 ◽  
Vol 30 (7) ◽  
pp. 2557-2569 ◽  
Author(s):  
Brant M. Wagener ◽  
Meng Hu ◽  
Anni Zheng ◽  
Xueke Zhao ◽  
Pulin Che ◽  
...  
Keyword(s):  
Vascular Permeability ◽  
Wiskott Aldrich Syndrome ◽  
Syndrome Protein ◽  
Lung Vascular Permeability ◽  
Tgf Β1

scholarly journals Neuronal Wiskott-Aldrich syndrome protein (N-WASP) is critical for formation of α-smooth muscle actin filaments during myofibroblast differentiation

2012 ◽  
Vol 303 (8) ◽  
pp. L692-L702 ◽  
Author(s):  
Guo-Qiang Cai ◽  
Chu-Fang Chou ◽  
Meng Hu ◽  
Anni Zheng ◽  
Louis F. Reichardt ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Actin ◽  
Critical Role ◽  
Lung Fibroblasts ◽  
Myofibroblast Differentiation ◽  
Muscle Actin ◽  
Wiskott Aldrich Syndrome ◽  
Cytoplasmic Filaments ◽  
Syndrome Protein ◽  
Tgf Β1

Myofibroblasts are implicated in pathological stromal responses associated with lung fibrosis. One prominent phenotypic marker of fully differentiated myofibroblasts is the polymerized, thick cytoplasmic filaments containing newly synthesized α-smooth muscle actin (α-SMA). These α-SMA-containing cytoplasmic filaments are important for myofibroblast contractility during tissue remodeling. However, the molecular mechanisms regulating the formation and maturation of α-SMA-containing filaments have not been defined. This study demonstrates a critical role for neuronal Wiskott-Aldrich syndrome protein (N-WASP) in regulating the formation of α-SMA-containing cytoplasmic filaments during myofibroblast differentiation and in myofibroblast contractility. Focal adhesion kinase (FAK) is activated by transforming growth factor-β1 (TGF-β1) and is required for phosphorylation of tyrosine residue 256 (Y256) of N-WASP. Phosphorylation of Y256 of N-WASP is essential for TGF-β1-induced formation of α-SMA-containing cytoplasmic filaments in primary human lung fibroblasts. In addition, we demonstrate that actin-related protein (Arp) 2/3 complex is downstream of N-WASP and mediates the maturation of α-SMA-containing cytoplasmic filaments. Together, this study supports a critical role of N-WASP in integrating FAK and Arp2/3 signaling to mediate formation of α-SMA-containing cytoplasmic filaments during myofibroblast differentiation and maturation.

scholarly journals The Novel Adaptor Protein, Mti1p, and Vrp1p, a Homolog of Wiskott-Aldrich Syndrome Protein-Interacting Protein (WIP), May Antagonistically Regulate Type I Myosins in Saccharomyces cerevisiae

Genetics ◽  
2002 ◽  
Vol 160 (3) ◽  
pp. 923-934
Author(s):  
Junko Mochida ◽  
Takaharu Yamamoto ◽  
Konomi Fujimura-Kamada ◽  
Kazuma Tanaka
Keyword(s):  
Adaptor Protein ◽  
Actin Binding ◽  
Temperature Sensitive ◽  
Null Mutation ◽  
Type I ◽  
Cortical Actin ◽  
Tail Region ◽  
Interacting Protein ◽  
Wiskott Aldrich Syndrome ◽  
Syndrome Protein

Abstract Type I myosins in yeast, Myo3p and Myo5p (Myo3/5p), are involved in the reorganization of the actin cytoskeleton. The SH3 domain of Myo5p regulates the polymerization of actin through interactions with both Las17p, a homolog of mammalian Wiskott-Aldrich syndrome protein (WASP), and Vrp1p, a homolog of WASP-interacting protein (WIP). Vrp1p is required for both the localization of Myo5p to cortical patch-like structures and the ATP-independent interaction between the Myo5p tail region and actin filaments. We have identified and characterized a new adaptor protein, Mti1p (Myosin tail region-interacting protein), which interacts with the SH3 domains of Myo3/5p. Mti1p co-immunoprecipitated with Myo5p and Mti1p-GFP co-localized with cortical actin patches. A null mutation of MTI1 exhibited synthetic lethal phenotypes with mutations in SAC6 and SLA2, which encode actin-bundling and cortical actin-binding proteins, respectively. Although the mti1 null mutation alone did not display any obvious phenotype, it suppressed vrp1 mutation phenotypes, including temperature-sensitive growth, abnormally large cell morphology, defects in endocytosis and salt-sensitive growth. These results suggest that Mti1p and Vrp1p antagonistically regulate type I myosin functions.

NMR Analyses of the Activation of the Arp2/3 Complex by Neuronal Wiskott−Aldrich Syndrome Protein†

Biochemistry ◽  
2005 ◽  
Vol 44 (46) ◽  
pp. 15247-15256 ◽  
Author(s):  
Mara Kreishman-Deitrick ◽  
Erin D. Goley ◽  
Lyle Burdine ◽  
Carilee Denison ◽  
Coumaran Egile ◽  
...  
Keyword(s):  
Wiskott Aldrich Syndrome ◽  
Syndrome Protein

scholarly journals Fyn and PTP-PEST–mediated Regulation of Wiskott-Aldrich Syndrome Protein (WASp) Tyrosine Phosphorylation Is Required for Coupling T Cell Antigen Receptor Engagement to WASp Effector Function and T Cell Activation

2004 ◽  
Vol 199 (1) ◽  
pp. 99-112 ◽  
Author(s):  
Karen Badour ◽  
Jinyi Zhang ◽  
Fabio Shi ◽  
Yan Leng ◽  
Michael Collins ◽  
...  
Keyword(s):  
T Cell ◽  
Tyrosine Phosphorylation ◽  
T Cell Activation ◽  
Actin Polymerization ◽  
Cell Activation ◽  
Synapse Formation ◽  
Tyrosine Phosphatase ◽  
Structural Constraints ◽  
Wiskott Aldrich Syndrome ◽  
Syndrome Protein

Involvement of the Wiskott-Aldrich syndrome protein (WASp) in promoting cell activation requires its release from autoinhibitory structural constraints and has been attributed to WASp association with activated cdc42. Here, however, we show that T cell development and T cell receptor (TCR)-induced proliferation and actin polymerization proceed normally in WASp−/− mice expressing a WASp transgene lacking the cdc42 binding domain. By contrast, mutation of tyrosine residue Y291, identified here as the major site of TCR-induced WASp tyrosine phosphorylation, abrogated induction of WASp tyrosine phosphorylation and its effector activities, including nuclear factor of activated T cell transcriptional activity, actin polymerization, and immunological synapse formation. TCR-induced WASp tyrosine phosphorylation was also disrupted in T cells lacking Fyn, a kinase shown here to bind, colocalize with, and phosphorylate WASp. By contrast, WASp was tyrosine dephosphorylated by protein tyrosine phosphatase (PTP)-PEST, a tyrosine phosphatase shown here to interact with WASp via proline, serine, threonine phosphatase interacting protein (PSTPIP)1 binding. Although Fyn enhanced WASp-mediated Arp2/3 activation and was required for synapse formation, PTP-PEST combined with PSTPIP1 inhibited WASp-driven actin polymerization and synapse formation. These observations identify key roles for Fyn and PTP-PEST in regulating WASp and imply that inducible WASp tyrosine phosphorylation can occur independently of cdc42 binding, but unlike the cdc42 interaction, is absolutely required for WASp contributions to T cell activation.

scholarly journals Wiskott–Aldrich syndrome protein (WASP) is a tumor suppressor in T cell lymphoma

2018 ◽  
Vol 25 (1) ◽  
pp. 130-140 ◽  
Author(s):  
Matteo Menotti ◽  
Chiara Ambrogio ◽  
Taek-Chin Cheong ◽  
Chiara Pighi ◽  
Ines Mota ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Suppressor ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Wiskott Aldrich Syndrome ◽  
Syndrome Protein

scholarly journals CD44 and β3 Integrin Organize Two Functionally Distinct Actin-based Domains in Osteoclasts

2007 ◽  
Vol 18 (12) ◽  
pp. 4899-4910 ◽  
Author(s):  
Anne Chabadel ◽  
Inmaculada Bañon-Rodríguez ◽  
David Cluet ◽  
Brian B. Rudkin ◽  
Bernhard Wehrle-Haller ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Actin Cytoskeleton ◽  
Interacting Protein ◽  
Wiskott Aldrich Syndrome ◽  
Diffuse Cloud ◽  
Sealing Zone ◽  
Β3 Integrin ◽  
Syndrome Protein

The actin cytoskeleton of mature osteoclasts (OCs) adhering to nonmineralized substrates is organized in a belt of podosomes reminiscent of the sealing zone (SZ) found in bone resorbing OCs. In this study, we demonstrate that the belt is composed of two functionally different actin-based domains: podosome cores linked with CD44, which are involved in cell adhesion, and a diffuse cloud associated with β3 integrin, which is involved in cell adhesion and contraction. Wiskott Aldrich Syndrome Protein (WASp) Interacting Protein (WIP)−/− OCs were devoid of podosomes, but they still exhibited actin clouds. Indeed, WIP−/− OCs show diminished expression of WASp, which is required for podosome formation. CD44 is a novel marker of OC podosome cores and the first nonintegrin receptor detected in these structures. The importance of CD44 is revealed by showing that its clustering restores podosome cores and WASp expression in WIP−/− OCs. However, although CD44 signals are sufficient to form a SZ, the presence of WIP is indispensable for the formation of a fully functional SZ.

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