Sprouty Proteins Inhibit Receptor-mediated Activation of Phosphatidylinositol-specific Phospholipase C

Akbulut, Simge; Reddi, Alagarsamy Lakku; Aggarwal, Priya; Ambardekar, Charuta; Canciani, Barbara; Kim, Marianne K.H.; Hix, Laura M.; Vilimas, Tomas; Mason, Jacqueline M.; Basson, M. Albert; Lovatt, Matthew; Powell, Jonathan D.; Collins, Samuel; Quatela, Steven; Philips, Mark R.; Licht, Jonathan D.

doi:10.1091/mbc.e10-02-0123

Cited by 44 publications

(48 citation statements)

References 70 publications

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“…This suggests that Spry4 most likely acts via the PLC-Ca ++ and not the Ras pathway, leading to both inhibition of Ca 2+ mobilisation and inhibition of Erk activation via PKC. It has also recently been shown that murine Spry1 and Spry2 can bind PLC thereby inhibiting the production of IP3 and calcium release in NIH3T3 cells, and that they regulate PLC activity in T cells (Akbulut et al, 2010). Together with our data, these studies suggest that regulation of the PLC-Ca 2+ pathway by Spry proteins plays important roles in various biological contexts.…”

Section: Regulation Of Branching Morphogenesis By Spry Proteinssupporting

confidence: 84%

Characterisation of a new regulator of BDNF signalling, Sprouty3, involved in axonal morphogenesis in vivo

et al. 2010

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SUMMARYDuring development, many organs, including the kidney, lung and mammary gland, need to branch in a regulated manner to be functional. Multicellular branching involves changes in cell shape, proliferation and migration. Axonal branching, however, is a unicellular process that is mediated by changes in cell shape alone and as such appears very different to multicellular branching. Sprouty (Spry) family members are well-characterised negative regulators of Receptor tyrosine kinase (RTK) signalling. Knockout of Spry1, 2 and 4 in mouse result in branching defects in different organs, indicating an important role of RTK signalling in controlling branching pattern. We report here that Spry3, a previously uncharacterised member of the Spry family plays a role in axonal branching. We found that spry3 is expressed specifically in the trigeminal nerve and in spinal motor and sensory neurons in a Brain-derived neurotrophin factor (BDNF)-dependent manner. Knockdown of Spry3 expression causes an excess of axonal branching in spinal cord motoneurons in vivo. Furthermore, Spry3 inhibits the ability of BDNF to induce filopodia in Xenopus spinal cord neurons. Biochemically, we show that Spry3 represses calcium release downstream of BDNF signalling. Altogether, we have found that Spry3 plays an important role in the regulation of axonal branching of motoneurons in vivo, raising the possibility of unexpected conservation in the involvement of intracellular regulators of RTK signalling in multicellular and unicellular branching.

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Section: Regulation Of Branching Morphogenesis By Spry Proteinssupporting

confidence: 84%

Characterisation of a new regulator of BDNF signalling, Sprouty3, involved in axonal morphogenesis in vivo

et al. 2010

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“…All sprouty proteins were found to be negative regulators of growth factor signaling, especially the MAPK/ERK pathway (32,33). A potential role of sprouty proteins has been seen in T cell activation where both SPRY1 and SPRY2 inhibit T cell activation and IL-2 production (34,38). SPRY1-deficient mice have been shown to have enhanced antitumor T cell responses (39).…”

Section: Discussionmentioning

confidence: 99%

“…Sprouty proteins are a well-conserved family known to mediate the negative feedback regulation of the MAPK pathway (31,32). Sprouty proteins bind to Grb2 and other components of the MAPK pathway, preventing the upregulation of pERK (33,34).…”

Section: Figurementioning

confidence: 99%

Sprouty-2 regulates HIV-specific T cell polyfunctionality

et al. 2013

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The ability of individual T cells to perform multiple effector functions is crucial for protective immunity against viruses and cancer. This polyfunctionality is frequently lost during chronic infections; however, the molecular mechanisms driving T cell polyfunctionality are poorly understood. We found that human T cells stimulated by a high concentration of antigen lacked polyfunctionality and expressed a transcription profile similar to that of exhausted T cells. One specific pathway implicated by the transcription profile in control of T cell polyfunctionality was the MAPK/ERK pathway. This pathway was altered in response to different antigen concentrations, and polyfunctionality correlated with upregulation of phosphorylated ERK. T cells that were stimulated with a high concentration of antigen upregulated sprouty-2 (SPRY2), a negative regulator of the MAPK/ERK pathway. The clinical relevance of SPRY2 was confirmed by examining SPRY2 expression in HIV-specific T cells, where high levels of SPRY2 were seen in HIV-specific T cells and inhibition of SPRY2 expression enhanced the HIV-specific polyfunctional response independently of the PD-1 pathway. Our findings indicate that increased SPRY2 expression during chronic viral infection reduces T cell polyfunctionality and identify SPRY2 as a potential target for immunotherapy.

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“…An antibody against human Spry4 was purchased from Santa Cruz Biotechnology, Inc. (Santa Cruz, CA). Antibodies against mouse Spry1 and Spry2 have been previously described (23). Antibodies against the phosphorylated forms of STAT1, STAT3, ERK1/2 (Thr-202/Tyr-204), and p38 MAPK (Thr-180/Tyr-182), as well as antibodies against ERK1/2 and p38 MAPK, were obtained from Cell Signaling Technology (Danvers, MA).…”

Section: Methodsmentioning

confidence: 99%

Sprouty Proteins Are Negative Regulators of Interferon (IFN) Signaling and IFN-inducible Biological Responses

Sharma

Joshi

Sassano

et al. 2012

Journal of Biological Chemistry

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Background:The potential involvement of Spry proteins in IFN signaling is unknown. Results: Type I IFN treatment results in up-regulation of Spry proteins, which negatively control generation of IFN responses. Conclusion: Spry proteins play important regulatory roles in IFN signaling and the generation of the biological effects of IFNs. Significance: This study provides evidence for the existence of a key signaling pathway that controls IFN responses.

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Sprouty Proteins Inhibit Receptor-mediated Activation of Phosphatidylinositol-specific Phospholipase C

Cited by 44 publications

References 70 publications

Characterisation of a new regulator of BDNF signalling, Sprouty3, involved in axonal morphogenesis in vivo

Characterisation of a new regulator of BDNF signalling, Sprouty3, involved in axonal morphogenesis in vivo

Sprouty-2 regulates HIV-specific T cell polyfunctionality

Sprouty Proteins Are Negative Regulators of Interferon (IFN) Signaling and IFN-inducible Biological Responses

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