SIN1 / MAPKAP1
Essential structural subunit of mTORC2 (stress-activated protein kinase-interacting protein 1). Required for mTORC2 assembly and integrity; controls the substrate specificity of mTORC2 toward Akt and other AGC kinases. Prolonged rapamycin treatment can disrupt SIN1-containing mTORC2 in some cell types but not others, which is one explanation for the impaired Akt signalling seen with chronic rapamycin.
mTORC2's growth-factor antenna. A structural building block that mTORC2 (the second mTOR complex) needs in order to assemble and work properly. Long-term rapamycin use can eventually break apart mTORC2 that contains it, part of why chronic rapamycin can dull Akt signaling.
MAPKAP1. The PH domain inhibits mTORC2 until PIP3 relieves it – the cleanest mechanism for how growth factors reach mTORC2.
TL;DR. SIN1 / MAPKAP1 appears in 4 curated studies in Oliver's mTOR Atlas: 4 at the molecular level (cells, biochemistry, structure). No study in people is recorded for it in the Atlas yet. It has 1 interaction in the curated pathway model.
In the pathway model
| Interaction | Mechanism | Evidence | Studies |
|---|---|---|---|
| SIN1 / MAPKAP1 required-for mTORC2 mechanism: complex-assembly · this link in full · on the map table | SIN1 holds mTORC2 together and positions its target – without it, mTORC2 can't switch Akt on. SIN1 holds the complex together and positions the substrate; without it mTORC2 cannot phosphorylate Akt. SIN1 holds the complex together and positions the substrate; without it mTORC2 cannot phosphorylate Akt. Holds under: Mammalian cell studies and a cryo-EM structure (JAC2006, FRI2006, YAN2006, STU2018). Cell and structural evidence; not tested in people by these sources. plausible in people, not shown directly · settled in the literature | M | JAC2006, FRI2006, YAN2006, STU2018 |
Evidence at a glance
| Evidence | What it means | Studies |
|---|---|---|
| M | Molecular — cells, biochemistry, structure | 4 |
No direct human evidence in the Atlas for this entity yet — everything below rests on animal or molecular work.
Studies
| Year | Evidence | Study |
|---|---|---|
| 2018 | M | Architecture of the human mTORC2 core complex STU2018 Architecture of the human mTORC2 core complex (mTOR-Rictor-SIN1-mLST8). |
| 2006 | M | mSin1 is necessary for Akt/PKB phosphorylation, and its isoforms define three distinct mTORC2s FRI2006 mSin1 is required for mTORC2 assembly and Akt Ser473 phosphorylation; isoforms define distinct complexes. |
| 2006 | M | SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity JAC2006 SIN1 maintains rictor-mTOR integrity and confers mTORC2 Akt-Ser473 kinase activity and substrate specificity. |
| 2006 | M | Identification of Sin1 as an essential TORC2 component required for complex formation and kinase activity YAN2006 Identified Sin1 as an essential TORC2 component required for Akt phosphorylation. |
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