TGFβ receptor endocytosis and Smad signaling require synaptojanin1, PI3K–C2α-, and INPP4B-mediated phosphoinositide conversions

Aki, Sho; Yoshioka, Kazuaki; Takuwa, Noriko; Takuwa, Yoh

doi:10.1091/mbc.e19-11-0662

Cited by 22 publications

(23 citation statements)

References 48 publications

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“…At the clathrin lattice, PI3K-C2α metabolizes PI(4,5)P2 to PI(3,4)P2 in cooperation with the PI-5 0 -phosphatases ORCL and synaptojanin-1 [35,42]. Localized enrichments in PI(3,4)P2 enable the recruitment of endocytic accessory proteins such as sorting nexin-9, which interact with actin-branching activator Arp2/3 and dynamin, and ultimately generate constricting force at the neck of the CCPs [43][44][45][46] (Figure 3).…”

Section: Cellular Functions Of Class II Pi3k Isoformsmentioning

confidence: 99%

Class II phosphatidylinositol 3-kinase isoforms in vesicular trafficking

Yoshioka

2021

Biochemical Society Transactions

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Phosphatidylinositol 3-kinases (PI3Ks) are critical regulators of many cellular processes including cell survival, proliferation, migration, cytoskeletal reorganization, and intracellular vesicular trafficking. They are a family of lipid kinases that phosphorylate membrane phosphoinositide lipids at the 3′ position of their inositol rings, and in mammals they are divided into three classes. The role of the class III PI3K Vps34 is well-established, but recent evidence suggests the physiological significance of class II PI3K isoforms in vesicular trafficking. This review focuses on the recently discovered functions of the distinct PI3K-C2α and PI3K-C2β class II PI3K isoforms in clathrin-mediated endocytosis and consequent endosomal signaling, and discusses recently reported data on class II PI3K isoforms in different physiological contexts in comparison with class I and III isoforms.

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Section: Cellular Functions Of Class II Pi3k Isoformsmentioning

confidence: 99%

Class II phosphatidylinositol 3-kinase isoforms in vesicular trafficking

Yoshioka

2021

Biochemical Society Transactions

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“…prevented the activation of the TGF-induced transcriptional modulators Smad2/3 required for vascular integrity [87,89]. Collectively, these findings support a key role for PI3KC2 in endothelial cell function and angiogenesis that largely relates to its role in receptor CME.…”

Section: Accepted Articlementioning

confidence: 51%

“…PI3KC2 was also found to be essential for sphingosine 1-phosphate (S1P) receptor-1 mediated endothelial cell migration through PI(3)P-mediated activation of endosomal Rac1 ( Figure 4F) [86]. Moreover, PI3KC2 is required for the transforming growth factor  (TGF)-induced internalization of TGF receptors via CME in endothelial cells ( Figure 4E) [87,88]. TGF stimulation was demonstrated to induce the recruitment of the PI(4,5)P 2 5'-phosphatase synaptojanin-1, leading to increased PI(4)P levels, followed by local PI(3,4)P 2 synthesis mediated by PI3KC2.…”

Section: Class II Pi3ks In Endothelial Cell Function and Angiogenesismentioning

confidence: 99%

The molecular mechanisms mediating class II PI 3‐kinase function in cell physiology

et al. 2021

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The phosphoinositide 3‐kinase (PI3K) family of lipid‐modifying enzymes plays vital roles in cell signaling and membrane trafficking through the production of 3‐phosphorylated phosphoinositides. Numerous studies have analyzed the structure and function of class I and class III PI3Ks. In contrast, we know comparably little about the structure and physiological functions of the class II enzymes. Only recent studies have begun to unravel their roles in development, endocytic and endolysosomal membrane dynamics, signal transduction, and cell migration, while the mechanisms that control their localization and enzymatic activity remain largely unknown. Here, we summarize our current knowledge of the class II PI3Ks and outline open questions related to their structure, enzymatic activity, and their physiological and pathophysiological functions.

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“…SMA and mother against decapentaplegic (MAD)-related proteins (SMADs) are intracellular components of TGF-ß signalling pathway. containing eight members as SMAD1-Smad8 respectively [20][21][22][23]. SMAD1 is a critical inducer of the EMT process.…”

Section: Discussionmentioning

confidence: 99%

A Novel Circular RNA circTADA2A Promotes Proliferation And Metastasis Of Ovarian Cancer Through Sponging miR-203

Wang

Jin

Wang

et al. 2021

Preprint

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BackgroundCircular RNAs (circRNAs), a new type of non-coding RNA, have been demonstrated to play critical roles in the progression of various of malignant cancers. In the present study, we identified a circRNA termed as circTADA2A which was hypothesized that may be significantly up-regulated in OC tissues and cell lines.ResultsThe results revealed that ectopic expression of circTADA2A promoted the cell proliferation, migration, invasion and colony formation ability of OC cells. Constantly, silencing of circTADA2A inhibited those of OC cells. Furthermore, we identified that circTADA2A was able to target miR-203 in OC cell. MiR-203 was able to reverse the oncogenic effect of circTADA2A on proliferation, migration and metastasis of OC cells through targeting SMAD1.ConclusionsWe reported that circTADA2A served as a competing endogenous RNA (ceRNA) to sponge miR-203 and blocked its regulation of SMAD1. These findings provide insights into OC progression and also potential new targets for diagnose or treatment of OC.

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TGFβ receptor endocytosis and Smad signaling require synaptojanin1, PI3K–C2α-, and INPP4B-mediated phosphoinositide conversions

Cited by 22 publications

References 48 publications

Class II phosphatidylinositol 3-kinase isoforms in vesicular trafficking

Class II phosphatidylinositol 3-kinase isoforms in vesicular trafficking

The molecular mechanisms mediating class II PI 3‐kinase function in cell physiology

A Novel Circular RNA circTADA2A Promotes Proliferation And Metastasis Of Ovarian Cancer Through Sponging miR-203

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TGFβ receptor endocytosis and Smad signaling require synaptojanin1, PI3K–C2α-, and INPP4B-mediated phosphoinositide conversions

Cited by 22 publications

References 48 publications

Class II phosphatidylinositol 3-kinase isoforms in vesicular trafficking

Class II phosphatidylinositol 3-kinase isoforms in vesicular trafficking

The molecular mechanisms mediating class II PI 3‐kinase function in cell physiology

A Novel Circular RNA&nbsp;circTADA2A&nbsp;Promotes Proliferation And Metastasis Of Ovarian Cancer Through Sponging miR-203

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A Novel Circular RNA circTADA2A Promotes Proliferation And Metastasis Of Ovarian Cancer Through Sponging miR-203