Cell Signaling by Receptor Tyrosine Kinases

Lemmon, Mark A.; Schlessinger, Joseph

doi:10.1016/j.cell.2010.06.011

Cited by 4,831 publications

(3,793 citation statements)

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“…Upon binding of its ligand (epidermal growth factor, EGF) the receptor undergoes a conformational change into an open conformation allowing association of two EGFR molecules into a dimer. Dimerization then leads to autophosphorylation of tyrosine residues in the intracellular domain (4)(5)(6). This model has been supported by crystal structures of the extracellular domain of EGFR (7,8) as well as by reports of EGFR dimerization after stimulation with EGF.…”

Section: Introductionmentioning

confidence: 69%

“…The existence of preformed dimers, their relative amount in resting cells, and their role in EGFR signaling continue to present open questions and the findings of individual studies differ considerably (9,14). While some authors report negligible amounts of preformed dimers (15), others have found most EGFR molecules in dimeric form (6,9,16,17). Nagy et al (18) observed preformed dimers only at high expression levels of EGFR of ~600,000 receptors per cell.…”

Section: Introductionmentioning

confidence: 99%

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The Epidermal Growth Factor Receptor Forms Location-Dependent Complexes in Resting Cells

Yavas

Macháň

Wohland

2016

Biophysical Journal

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The epidermal growth factor receptor (EGFR) is a prototypical receptor tyrosine kinase involved in cell growth and proliferation and associated with various cancers. It is commonly assumed that after activation by binding of epidermal growth factor to the extracellular domain it dimerizes, followed by autophosphorylation of tyrosine residues at the intracellular domain. However, its oligomerization state before activation is controversial. In the absence of ligands, EGFR has been found in various, inconsistent amounts of monomeric, inactive dimeric, and oligomeric forms. In addition, evidence suggests that the active conformation is not a simple dimer but contains higher oligomers. As experiments in the past have been conducted at different conditions, we investigate here the influence of cell lines (HEK293, COS-7, and CHO-K1), temperature (room temperature and 37 C), and membrane localization on the quantitation of preformed dimers using SW-FCCS, DC-FCCS, quasi PIE-FCCS, and imaging FCCS. While measurement modality, temperature, and localization on upper or lower membranes have only a limited influence on the dimerization amount observed, the cell line and location to periphery versus center of the cell can change dimerization results significantly. The observed dimerization amount is strongly dependent on the expression level of endogenous EGFR in a cell line and shows a strong cell-to-cell variability even within the same cell line. In addition, using imaging FCCS, we find that dimers have a tendency to be found at the periphery of cells compared to central positions.

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Section: Introductionmentioning

confidence: 69%

Section: Introductionmentioning

confidence: 99%

The Epidermal Growth Factor Receptor Forms Location-Dependent Complexes in Resting Cells

Yavas

Macháň

Wohland

2016

Biophysical Journal

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“…Studies showed that this gene plays a pivotal role in a variety of biology processes in both prokaryotes and eukaryotes, including cell signalling [35], cell division, protein export, membrane transport, DNA repair, and multidrug resistance in tumours [36,37]. The functional range of the nucleotide binding protein family is gradually expanding with the accession of some new members.…”

Section: Discussionmentioning

confidence: 99%

Acid-resistant genes of oral plaque microbiome from the functional metagenomics

Zhang

Zheng

et al. 2018

Journal of Oral Microbiology

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Acid resistance is one of key properties assisting the survival of cariogenic bacteria in a dental caries environment, but only a few genes conferring acid resistance have been identified to data. Functional metagenomics provides a systematic method for investigating commensal DNA to identify genes that encode target functions. Here, the host strain Escherichia coli DH10B and a constructed bidirectional transcription vector pSKII+-lacZ contributed to the construction of a metagenomic library, and 46.6 Mb of metagenomic DNA was cloned from carious supragingival plaque of 8children along with screening for lethal functionality. The screen identified 2 positive clones that exhibited a similar aciduric phenotype to that of the positive controls. Bioinformatic analysis revealed that these two genes encoded an ATP/GTP-binding protein and a malate dehydrogenase. Moreover, we also performed functional screening of Streptococcus mutans, since it is one of the predominant cariogenic strains but was not identified in our initial screening. Five positive clones were retrieved. In conclusion, our improved functional metagenomics screening method helped in the identification of important acid resistance genes, thereby providing new insights into the mechanism underlying caries formation as well as in the prevention and treatment of early childhood caries (ECC).

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“…All RTKs possess a similar molecular architecture with three key features: an extracellular ligand binding domain, a transmembrane domain and a cytoplasmic kinase domain. In the human genome there are 58 known RTKs which are subdivided in 20 families according to structure of their extracellular domain (For review see [3]). RTKs function to transduce signals from extracellular stimuli by inducing changes in tyrosine phosphorylation that promote the formation of signaling complexes leading to changes in biological processes.…”

Section: Introductionmentioning

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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Cell Signaling by Receptor Tyrosine Kinases

Cited by 4,831 publications

References 144 publications

The Epidermal Growth Factor Receptor Forms Location-Dependent Complexes in Resting Cells

The Epidermal Growth Factor Receptor Forms Location-Dependent Complexes in Resting Cells

Acid-resistant genes of oral plaque microbiome from the functional metagenomics

SOCS proteins in regulation of receptor tyrosine kinase signaling

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