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T cell receptor-dependent activation of mTOR signaling in T cells is mediated by Carma1 and MALT1, but not Bcl10.

Publication ,  Journal Article
Hamilton, KS; Phong, B; Corey, C; Cheng, J; Gorentla, B; Zhong, X; Shiva, S; Kane, LP
Published in: Sci Signal
June 10, 2014

Signaling to the mechanistic target of rapamycin (mTOR) regulates diverse cellular processes, including protein translation, cellular proliferation, metabolism, and autophagy. Most models place Akt upstream of the mTOR complex, mTORC1; however, in T cells, Akt may not be necessary for mTORC1 activation. We found that the adaptor protein Carma1 [caspase recruitment domain (CARD)-containing membrane-associated protein 1] and at least one of its associated proteins, the paracaspase MALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1), were required for optimal activation of mTOR in T cells in response to stimulation of the T cell receptor (TCR) and the co-receptor CD28. However, Bcl10, which binds to Carma1 and MALT1 to form a complex that mediates signals from the TCR to the transcription factor NF-κB (nuclear factor κB), was not required. The catalytic activity of MALT1 was required for the proliferation of stimulated CD4+ T cells, but not for early TCR-dependent activation events. Consistent with an effect on mTOR, MALT1 activity was required for the increased metabolic flux in activated CD4+ T cells. Together, our data suggest that Carma1 and MALT1 play previously unappreciated roles in the activation of mTOR signaling in T cells after engagement of the TCR.

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Published In

Sci Signal

DOI

EISSN

1937-9145

Publication Date

June 10, 2014

Volume

7

Issue

329

Start / End Page

ra55

Location

United States

Related Subject Headings

  • TOR Serine-Threonine Kinases
  • Signal Transduction
  • Receptors, Antigen, T-Cell
  • Neoplasm Proteins
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
  • Mice
  • Cell Proliferation
  • Caspases
  • CD4-Positive T-Lymphocytes
  • CARD Signaling Adaptor Proteins
 

Citation

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Hamilton, K. S., Phong, B., Corey, C., Cheng, J., Gorentla, B., Zhong, X., … Kane, L. P. (2014). T cell receptor-dependent activation of mTOR signaling in T cells is mediated by Carma1 and MALT1, but not Bcl10. Sci Signal, 7(329), ra55. https://doi.org/10.1126/scisignal.2005169
Hamilton, Kristia S., Binh Phong, Catherine Corey, Jing Cheng, Balachandra Gorentla, Xiaoping Zhong, Sruti Shiva, and Lawrence P. Kane. “T cell receptor-dependent activation of mTOR signaling in T cells is mediated by Carma1 and MALT1, but not Bcl10.Sci Signal 7, no. 329 (June 10, 2014): ra55. https://doi.org/10.1126/scisignal.2005169.
Hamilton KS, Phong B, Corey C, Cheng J, Gorentla B, Zhong X, et al. T cell receptor-dependent activation of mTOR signaling in T cells is mediated by Carma1 and MALT1, but not Bcl10. Sci Signal. 2014 Jun 10;7(329):ra55.
Hamilton, Kristia S., et al. “T cell receptor-dependent activation of mTOR signaling in T cells is mediated by Carma1 and MALT1, but not Bcl10.Sci Signal, vol. 7, no. 329, June 2014, p. ra55. Pubmed, doi:10.1126/scisignal.2005169.
Hamilton KS, Phong B, Corey C, Cheng J, Gorentla B, Zhong X, Shiva S, Kane LP. T cell receptor-dependent activation of mTOR signaling in T cells is mediated by Carma1 and MALT1, but not Bcl10. Sci Signal. 2014 Jun 10;7(329):ra55.

Published In

Sci Signal

DOI

EISSN

1937-9145

Publication Date

June 10, 2014

Volume

7

Issue

329

Start / End Page

ra55

Location

United States

Related Subject Headings

  • TOR Serine-Threonine Kinases
  • Signal Transduction
  • Receptors, Antigen, T-Cell
  • Neoplasm Proteins
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
  • Mice
  • Cell Proliferation
  • Caspases
  • CD4-Positive T-Lymphocytes
  • CARD Signaling Adaptor Proteins