Structural and functional diversity of adaptor proteins involved in tyrosine kinase signalling

Csiszár, Ágnes

doi:10.1002/bies.20411

Cited by 27 publications

(19 citation statements)

References 101 publications

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“…Such a mechanism of action could explain the finding that CaM is not able to activate NtMKP1 (65), since its function could be to transmit the Ca 2ϩ signal to a presently as yet unknown third protein. This would allow CaM to act as a Ca 2ϩ -dependent "adaptor" protein, similar to the adaptor proteins that organize large protein complexes in transmembrane protein kinase signaling (66,67). MAPKs are also known as structural adaptors in the formation of transcription complexes (68).…”

Section: Ntmkp1-bmentioning

confidence: 99%

Calcium-dependent and -independent Binding of Soybean Calmodulin Isoforms to the Calmodulin Binding Domain of Tobacco MAPK Phosphatase-1

Rainaldi

Yamniuk

Murase

et al. 2007

Journal of Biological Chemistry

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The recent finding of an interaction between calmodulin (CaM) and the tobacco mitogen-activated protein kinase phosphatase-1 (NtMKP1) establishes an important connection between Ca 2؉ signaling and the MAPK cascade, two of the most important signaling pathways in plant cells. Here we have used different biophysical techniques, including fluorescence and NMR spectroscopy as well as microcalorimetry, to characterize the binding of soybean CaM isoforms, SCaM-1 and -4, to synthetic peptides derived from the CaM binding domain of NtMKP1. We find that the actual CaM binding region is shorter than what had previously been suggested. Moreover, the peptide binds to the SCaM C-terminal domain even in the absence of free Ca 2؉ with the single Trp residue of the NtMKP1 peptides buried in a solvent-inaccessible hydrophobic region. In the presence of Ca 2؉ , the peptides bind first to the C-terminal lobe of the SCaMs with a nanomolar affinity, and at higher peptide concentrations, a second peptide binds to the N-terminal domain with lower affinity. Thermodynamic analysis demonstrates that the formation of the peptide-bound complex with the Ca 2؉ -loaded SCaMs is driven by favorable binding enthalpy due to a combination of hydrophobic and electrostatic interactions. Experiments with CaM proteolytic fragments showed that the two domains bind the peptide in an independent manner. To our knowledge, this is the first report providing direct evidence for sequential binding of two identical peptides of a target protein to CaM. Discussion of the potential biological role of this interaction motif is also provided.

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Section: Ntmkp1-bmentioning

confidence: 99%

Calcium-dependent and -independent Binding of Soybean Calmodulin Isoforms to the Calmodulin Binding Domain of Tobacco MAPK Phosphatase-1

Rainaldi

Yamniuk

Murase

et al. 2007

Journal of Biological Chemistry

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“…Adaptor proteins have a variety of functional domains which mediate specific protein-protein and protein-lipid interactions. [1][2][3][4][5] For example, Src homology 2 (SH2) and phosphotyrosine binding (PTB) domains can bind to phosphotyrosine containing motifs. [6][7][8][9] Src homology 3 (SH3) domains recognize and bind to proline-rich sequences in their respective binding partners.…”

Section: Introductionmentioning

confidence: 99%

Adaptor Protein STAP-2 Modulates Cellular Signaling in Immune Systems

Sekine

2014

Biological & Pharmaceutical Bulletin

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Signal-transducing adaptor protein-2 (STAP-2) is a recently identified adaptor protein that contains a pleckstrin homology (PH), Src homology 2 (SH2)-like domains, and proline-rich regions in its C-terminal. STAP-2 belongs to a family of STAP adaptor proteins and plays a crucial role in a variety of cellular signal transduction pathways by interacting with signaling or transcriptional molecules. STAP-2, in particular, regulates both the innate and adaptive immune systems. STAP-2 functionally interacts with signal transducers and activators of transcription 3 (STAT3) and STAT5 in cytokine signaling pathways. In addition, STAP-2 also binds to myeloid differentiation factor 88 (MyD88) and inhibitor (I)κB kinase α/β (IKK-α/β) in Toll-like receptor4 (TLR4) signaling, and enhances the production of inflammatory cytokines in macrophages. More importantly, experiments using STAP-2 deficient mice show that STAP-2 modulates several T-cell functions such as cell motility, survival and death. It is also reported that STAP-2 controls the immunoglobulin E (IgE)-mediated allergy response. This accumulated evidence indicates that adaptor protein STAP-2 is an important modulator of both the innate and adaptive immune systems.

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“…They are composed of multiple protein-protein and/or protein-lipid interacting domains, through which they link signaling components to form macromolecular complexes and propagate cellular signals. 1,2 Depending on the functional role of the interacting partner, adaptor proteins can participate in the regulation of various signaling pathways. A number of adaptor proteins have been demonstrated to regulate tumorigenesis.…”

mentioning

confidence: 99%

XB130, a Novel Adaptor Protein, Promotes Thyroid Tumor Growth

Shiozaki

Lodyga

Bai

et al. 2011

The American Journal of Pathology

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Adaptor proteins with multimodular structures can participate in the regulation of various cellular functions. We have cloned a novel adaptor protein, XB130, which binds the p85␣ subunit of phosphatidyl inositol 3-kinase and subsequently mediates signaling through RET/ PTC in TPC-1 thyroid cancer cells. In the present study, we sought to determine the role of XB130 in the tumorigenesis in vivo and in related molecular mechanisms. In WRO thyroid cancer cells, knockdown of XB130 using small interfering RNA inhibited G 1 -S phase progression, induced spontaneous apoptosis, and enhanced intrinsic and extrinsic apoptotic stimulus-induced cell death. Growth of tumors in nude mice formed from XB130 shRNA stably transfected WRO cells were significantly reduced, with decreased cell proliferation and increased apoptosis. Microarray analysis identified 246 genes significantly changed in XB130 shRNA transfected cells. Among them, 57 genes are related to cell proliferation or survival, including many transcription regulators. Ingenuity Pathway Analysis showed that the topranked disease related to XB130 is cancer, and the top molecular and cellular functions are cellular growth and proliferation and cell cycle. A human thyroid tissue microarray study identified expression of XB130 in normal thyroid tissue as well as in human thyroid carcinomas. These observations suggest that the expression of XB130 in these cancer cells may affect cell proliferation and survival by controlling the expression of multiple genes, especially transcription regulators.

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Structural and functional diversity of adaptor proteins involved in tyrosine kinase signalling

Cited by 27 publications

References 101 publications

Calcium-dependent and -independent Binding of Soybean Calmodulin Isoforms to the Calmodulin Binding Domain of Tobacco MAPK Phosphatase-1

Calcium-dependent and -independent Binding of Soybean Calmodulin Isoforms to the Calmodulin Binding Domain of Tobacco MAPK Phosphatase-1

Adaptor Protein STAP-2 Modulates Cellular Signaling in Immune Systems

XB130, a Novel Adaptor Protein, Promotes Thyroid Tumor Growth

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