Multiple monoubiquitination of RTKs is sufficient for their endocytosis and degradation

Haglund, Kaisa; Sigismund, Sara; Polo, Simona; Szymkiewicz, Iwona; Fiore, Pier Paolo Di; Đikić, Ivan

doi:10.1038/ncb983

Cited by 747 publications

(721 citation statements)

References 29 publications

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“…Although mono-ubiquitination of RTKs lead to degradation in lysosomes [46], association of SOCS2 with FLT3 led to increased ubiquitination of FLT3, which was followed by degradation in the proteasomes. As SOCS2 directs FLT3 for proteasomal degradation it is expected that it will negatively regulate receptor signaling.…”

Section: Socs2mentioning

confidence: 99%

SOCS proteins in regulation of receptor tyrosine kinase signaling

Kazi

Kabir

Flores‐Morales

2014

Cell. Mol. Life Sci.

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SOCS proteins in regulation of receptor tyrosine kinase signaling.Uddin, Kazi; Kabir, Nuzhat N; Flores-Morales, Amilcar; Rönnstrand, Lars Link to publication Citation for published version (APA): Kazi, J. U., Kabir, N. N., Flores-Morales, A., & Rönnstrand, L. (2014). SOCS proteins in regulation of receptor tyrosine kinase signaling. Cellular and Molecular Life Sciences, 71(17), 3297-3310. DOI: 10.1007/s00018-014-1619-y General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. AbstractThe receptor tyrosine kinases (RTKs) are a family of cell surface receptors that play critical roles in signal transduction from extracellular stimuli. Many of this family of kinases are overexpressed or mutated in human malignancies and thus became attractive drug target for cancer treatment. The signaling mediated by RTKs must be tightly regulated by interacting proteins including protein-tyrosine phosphatases and ubiquitin ligases. The suppressor of cytokine signaling (SOCS) family proteins are well known negative regulators of cytokine receptors signaling consisting of eight structurally similar proteins, SOCS1-7 and CIS. A key feature of this family of proteins is the presence of an SH2 domain and a SOCS box. Recent studies suggest that SOCS proteins also play a role in RTK signaling. Activation of RTK results in transcriptional activation of SOCS encoding genes. These proteins associate with RTKs through their SH2 domains and subsequently recruit the E3 ubiquitin machinery through the SOCS box, and thereby limit receptor stability by inducing ubiquitination. In a similar fashion SOCS proteins negatively regulate mitogenic signaling by RTKs. It is also evident that RTKs sometimes can bypass SOCS regulation and SOCS proteins can even potentiate RTKs-mediated mitogenic signaling. Thus apart from negative regulation of receptor signaling, SOCS proteins may also influence signaling in other ways.

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Section: Socs2mentioning

confidence: 99%

SOCS proteins in regulation of receptor tyrosine kinase signaling

Kazi

Kabir

Flores‐Morales

2014

Cell. Mol. Life Sci.

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“…Growing evidence indicates that ubiquitination of RTKs is critical for their lysosomal degradation, through their ubiquitin-dependent targeting to intralumenal vesicles of MVBs and lysosomal degradation (Urbe et al, 2000;Raiborg et al, 2002;Duan et al, 2003;Jiang et al, 2003;Yamasaki et al, 2003). RTKs, including Met, may undergo multimonoubiquitination and Lys63-linked polyubiquitination, both of which do not form a signal for proteasomal degradation (Haglund et al, 2003;Mosesson et al, 2003;Carter et al, 2004;Huang et al, 2006). The ubiquitinated RTKs are selectively recognized by proteins of the endocytic pathway that contain ubiquitin-interacting domains (UBA, UIM, UEV and CUE), such as Epsin, Eps15, Stam and Hrs (HGF regulated tyrosine kinase substrate) among others.…”

Section: Regulation Of Met Downregulation: Consequence For Oncogenic mentioning

confidence: 99%

From Tpr-Met to Met, tumorigenesis and tubes

2007

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The receptor for hepatocyte growth factor (HGF)/scatter factor (SF), Met, controls a program of invasive epithelial growth through the coordination of cell proliferation and survival, cell migration and epithelial morphogenesis. This process is important during embryogenesis and for organ regeneration in the adult. However, when deregulated the HGF/SF-Met signaling axis contributes to tumorigenesis and metastasis. Studies on the oncogenic activation of the Met receptor have shed light on the molecular mechanisms underlying the oncogenic activation of receptor tyrosine kinase (RTKs). More than a decade ago, work on the Met related oncogene, Tpr-Met, revealed the mechanism for activation of RTK-derived oncogenes generated following chromosomal translocation. More recently, studies on the mechanisms of downregulation of the Met RTK highlight a role for loss of downregulation in RTK oncogenic activation.

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“…Given the role of ubiquitination during clathrinmediated endocytosis [Haglund et al, 2003], and the fact that other tyrosine kinase receptors are ubiquitinated upon endocytosis, our laboratory asked whether Met was ubiquitinated after incubation of cells with purified InlB, or upon infection of cells with Listeria [Veiga and Cossart, 2005]. Indeed, Met was monoubiquitinated upon InlB stimulation in a Cbl-dependent fashion, and purified InlB induced the endocytosis of Met.…”

Section: A Role For Clathrin During the Entry Of Listeria And Other Zmentioning

confidence: 99%

Cytoskeleton rearrangements during Listeria infection: Clathrin and septins as new players in the game

Mostowy

Cossart

2009

Cell Motil. Cytoskeleton

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The study of an infection process can reveal how microbes exploit the host, and can illuminate unknown host cellular functions. Invasive pathogens have evolved efficient strategies to promote their internalization within normally non-phagocytic host cells. The so-called ''zippering'' bacteria present to host cell receptors molecules that mimic endogenous ligands, thereby inducing specific intracellular signaling cascades ultimately resulting in actin polymerization and uptake. Here we review how the bacterial pathogen Listeria monocytogenes enters into cells, and present a series of studies revealing that in addition to actin rearrangements this bacterium exploits the clathrin-mediated endocytosis machinery together with septins, a novel cytoskeleton element. The challenge is now to decipher how all of these components orchestrate themselves to permit entry into normally non-phagocytic cells. Cell Motil. Cytoskeleton 66: 816-823, 2009. '

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Multiple monoubiquitination of RTKs is sufficient for their endocytosis and degradation

Cited by 747 publications

References 29 publications

SOCS proteins in regulation of receptor tyrosine kinase signaling

SOCS proteins in regulation of receptor tyrosine kinase signaling

From Tpr-Met to Met, tumorigenesis and tubes

Cytoskeleton rearrangements during Listeria infection: Clathrin and septins as new players in the game

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