SH3BP4 Is a Negative Regulator of Amino Acid-Rag GTPase-mTORC1 Signaling

Young Mi Kim, Matthew Stone, Tae Hyun Hwang, Yeon Gil Kim, Jane R. Dunlevy, Timothy J. Griffin, Do Hyung Kim

Research output: Contribution to journalArticle

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Abstract

Amino acids stimulate cell growth and suppress autophagy through activation of mTORC1. The activation of mTORC1 by amino acids is mediated by Rag guanosine triphosphatase (GTPase) heterodimers on the lysosome. The molecular mechanism by which amino acids regulate the Rag GTPase heterodimers remains to be elucidated. Here, we identify SH3 domain-binding protein 4 (SH3BP4) as a binding protein and a negative regulator of Rag GTPase complex. SH3BP4 binds to the inactive Rag GTPase complex through its Src homology 3 (SH3) domain under conditions of amino acid starvation and inhibits the formation of active Rag GTPase complex. As a consequence, the binding abrogates the interaction of mTORC1 with Rag GTPase complex and the recruitment of mTORC1 to the lysosome, thus inhibiting amino acid-induced mTORC1 activation and cell growth and promoting autophagy. These results demonstrate that SH3BP4 is a negative regulator of the Rag GTPase complex and amino acid-dependent mTORC1 signaling.

Original languageEnglish (US)
Pages (from-to)833-846
Number of pages14
JournalMolecular Cell
Volume46
Issue number6
DOIs
StatePublished - Jun 29 2012

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src Homology Domains
Guanosine
Carrier Proteins
Amino Acids
Autophagy
Lysosomes
Aminoacylation
Growth
Starvation
mechanistic target of rapamycin complex 1

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Kim, Y. M., Stone, M., Hwang, T. H., Kim, Y. G., Dunlevy, J. R., Griffin, T. J., & Kim, D. H. (2012). SH3BP4 Is a Negative Regulator of Amino Acid-Rag GTPase-mTORC1 Signaling. Molecular Cell, 46(6), 833-846. https://doi.org/10.1016/j.molcel.2012.04.007

SH3BP4 Is a Negative Regulator of Amino Acid-Rag GTPase-mTORC1 Signaling. / Kim, Young Mi; Stone, Matthew; Hwang, Tae Hyun; Kim, Yeon Gil; Dunlevy, Jane R.; Griffin, Timothy J.; Kim, Do Hyung.

In: Molecular Cell, Vol. 46, No. 6, 29.06.2012, p. 833-846.

Research output: Contribution to journalArticle

Kim, YM, Stone, M, Hwang, TH, Kim, YG, Dunlevy, JR, Griffin, TJ & Kim, DH 2012, 'SH3BP4 Is a Negative Regulator of Amino Acid-Rag GTPase-mTORC1 Signaling', Molecular Cell, vol. 46, no. 6, pp. 833-846. https://doi.org/10.1016/j.molcel.2012.04.007
Kim, Young Mi ; Stone, Matthew ; Hwang, Tae Hyun ; Kim, Yeon Gil ; Dunlevy, Jane R. ; Griffin, Timothy J. ; Kim, Do Hyung. / SH3BP4 Is a Negative Regulator of Amino Acid-Rag GTPase-mTORC1 Signaling. In: Molecular Cell. 2012 ; Vol. 46, No. 6. pp. 833-846.
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