FYVE fingers bind PtdIns(3)P

Gaullier, Jean Michel; Simonsen, Anne; D’Arrigo, Antonello; Bremnes, Bjørn; Stenmark, Harald; Aasland, Rein

doi:10.1038/28767

Cited by 527 publications

(443 citation statements)

References 10 publications

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“…The ring FYVE domains of EEA1, Vps27p and Vac1p fused to green¯uorescent protein are localized to membranes of an endocytic compartment in yeast, and this localization changes to be cytosolic in a Vps34p PI(3)K-de®cient mutant that completely lacks PtdIns(3)P (Burd & Emr 1998). These experimental observations indicate that the endosomal localization of these proteins is mediated through the binding of their ring FYVE domains to PtdIns(3)P. The ring FYVE domain of Hrs also binds speci®cally to PtdIns(3)P (Gaullier et al 1998). The early endosomal localization of Hrs appears to be mediated by this binding, because the ring FYVE domain of Hrs can replace that of EEA1 with respect to the endosomal targeting of EEA1 (Gaullier et al 1998).…”

Section: Discussionmentioning

confidence: 85%

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A Hrs binding protein having a Src homology 3 domain is involved in intracellular degradation of growth factors and their receptors

et al. 2000

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Background: Hrs (hepatocyte growth factor (HGF)-regulated tyrosine kinase substrate) is an early endosomal protein that is rapidly tyrosinephosphorylated in cells stimulated with growth factors. Hrs is thought to play a regulatory role in the endocytosis of growth factor/receptor complexes through early endosomes. In this study, we searched for Hrs-interacting molecules which may regulate the function of Hrs, using a yeast two-hybrid system.

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Section: Discussionmentioning

confidence: 85%

“…The ring FYVE domains of EEA1, Vps27p, Fab1p and Vac1p/Pep7p bind speci®cally to phosphatidylinositol 3-phosphate (PtdIns(3)P) (Burd & Emr 1998;Gaullier et al 1998;Patki et al 1998). Treatment of cells with phosphatidylinositol 3-OH kinase (PI(3)K) inhibitor wortmannin causes the dissociation of EEA1 from early endosomes (Patki et al 1997).…”

Section: Discussionmentioning

confidence: 99%

A Hrs binding protein having a Src homology 3 domain is involved in intracellular degradation of growth factors and their receptors

et al. 2000

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“…The two most important PtdIns3P-binding domains are the FYVE (Fab1, YOTB, Vac1 and EEA1) zinc finger domain [32] and the PH (phox-homology) domain [33]. Proteins with these domains play a role in sorting various ubiquitinated receptors from late endosomes to lysosomes.…”

Section: Discussionmentioning

confidence: 99%

Inhibitors of phosphoinositide 3-kinase cause defects in the postendocytic sorting of β2-adrenergic receptors

Awwad

Iyer

Rosenfeld

et al. 2007

Experimental Cell Research

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Phosphatidylinositol 3-kinase inhibitors have been shown to affect the endocytosis or subsequent intracellular sorting in various receptor systems. Agonist-activated β 2 -adrenergic receptors undergo desensitization by mechanisms that include the phosphorylation, endocytosis and degradation of receptors. Following endocytosis, most internalized receptors are sorted to the cell surface, but some proportion is sorted to lysosomes for degradation. It is not known what governs the ratio of receptors that recycle versus receptors that undergo degradation. To determine if phosphatidylinositol 3-kinases regulate β 2 -adrenergic receptor trafficking, HEK293 cells stably expressing these receptors were treated with the phosphatidylinositol 3-kinase inhibitors LY294002 or wortmannin. We then studied agonist-induced receptor endocytosis and postendocytic sorting, including recycling and degradation of the internalized receptors. Both inhibitors amplified the internalization of receptors after exposure to the β-agonist isoproterenol, which was attributable to the sorting of a significant fraction of receptors to an intracellular compartment from which receptor recycling did not occur. The initial rate of β 2 -adrenergic receptor endocytosis and the default rate of receptor recycling were not significantly altered. During prolonged exposure to agonist, LY294002 slowed the degradation rate of β 2 -adrenergic receptors and caused the accumulation of receptors within rab7-positive vesicles. These results suggest that phosphatidylinositol 3-kinase inhibitors (1) cause a misrouting of β 2 -adrenergic receptors into vesicles that are neither able to efficiently recycle to the surface nor sort to lysosomes, and (2) delays the movement of receptors from late endosomes to lysosomes.

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“…Hrs/ Hgs, another FYVE domain containing protein, was also shown to participate in Smad presentation to receptor and to synergize with SARA in stimulating TGF-b/Smad signaling (Miura et al, 2000). Hrs/Hgs binds phosphatidylinositol 3-phosphate (PtdIns(3)P) and is localized on early endosomes (Burd and Emr, 1998;Gaullier et al, 1998;Patki et al, 1998). These properties might be shared with SARA, which like Hrs/Hgs, has a punctate cytoplasmic staining pattern and binds PtdIns(3)P (Tsukazaki et al, 1998;Itoh et al, 2002).…”

Section: Regulation Of Smad Activation Tgf-b Receptor-induced Smad Acmentioning

confidence: 99%

Regulation of cell proliferation by Smad proteins

Dijke

Goumans

Itoh

2002

Journal Cellular Physiology

395

275

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Transforming growth factor-b (TGF-b) family members which include TGF-bs, activins, and bone morphogenetic proteins (BMPs) regulate a broad spectrum of biological responses on a large variety of cell types. TGF-b family members initiate their cellular responses by binding to distinct receptors with intrinsic serine/ threonine kinase activity and activation of speci®c downstream intracellular effectors termed Smad proteins. Smads relay the signal from the cell membrane to the nucleus, where they affect the transcription of target genes. Smad activation, subcellular distribution, and stability have been found to be intricately regulated and a broad array of transcription factors have been identi®ed as Smad partners. Important activities of TGF-b are its potent anti-mitogenic and pro-apoptotic effects that, at least in part, are mediated via Smad proteins. Escape from TGF-b/ Smad-induced growth inhibition and apoptosis is frequently observed in tumors. Certain Smads have been found to be mutated in speci®c types of cancer and gene ablation of particular Smads in mice has revealed increased rate of tumorigenesis. In late stage tumors, TGF-b has been shown to function as a tumor promoter. TGFb can stimulate the de-differentiation of epithelial cells to malignant invasive and metastatic ®broblastic cells. Interestingly, TGF-b may mediate these effects directly on tumor cells via subverted Smad-dependent and/or Smad-independent pathways.

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FYVE fingers bind PtdIns(3)P

Cited by 527 publications

References 10 publications

A Hrs binding protein having a Src homology 3 domain is involved in intracellular degradation of growth factors and their receptors

A Hrs binding protein having a Src homology 3 domain is involved in intracellular degradation of growth factors and their receptors

Inhibitors of phosphoinositide 3-kinase cause defects in the postendocytic sorting of β2-adrenergic receptors

Regulation of cell proliferation by Smad proteins

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