Reactome | p-S207 KARS1 dimer binds MITF-M:HINT1 dimer

p-S207 KARS1 dimer binds MITF-M:HINT1 dimer

Stable Identifier

R-HSA-9825782

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

p-S207 KARS1 dimer binds MITF-M:HINT1 dimer

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

Phosphorylation of serine 207 of KARS downstream of MAPK signaling promotes a conformational change that releases the lysyl-tRNA synthase from the multisynthetase complex and promotes its nuclear translocation. The conformational change additionally exposes a C-terminal region of KARS that facilitates interaction with MITF (Lee et al, 2004; Yannay-Cohen et al, 2009; Ofir-Birin et al, 2013). Conformational changes and interaction with MITF shift the activity of KARS1 away from tRNA amino-acylation towards synthesis of AP4A (P(1),P(4)-bis(5'-adenosyl) tetraphosphate(4-)). AP4A binds to the HINT1 and dissociates it from MITF, activating MITF-dependent transcription (Yannay-Cohen et al, 2009; Ofir-Birin et al, 2013; Genovese et al, 2012; Carmi-Levy et al, 2008; reviewed in Goding and Arnheiter, 2019).

Literature References

PubMed ID	Title	Journal	Year
14975237	The function of lysyl-tRNA synthetase and Ap4A as signaling regulators of MITF activity in FcepsilonRI-activated mast cells Lee, YN, Razin, E, Nechushtan, H, Figov, N	Immunity	2004
31123060	MITF-the first 25 years Arnheiter, H, Goding, CR	Genes Dev	2019
18644867	Diadenosine tetraphosphate hydrolase is part of the transcriptional regulation network in immunologically activated mast cells Razin, E, Nechushtan, H, Kay, G, Yannay-Cohen, N, Carmi-Levy, I	Mol Cell Biol	2008
23159739	Structural switch of lysyl-tRNA synthetase between translation and transcription Nechushtan, H, Fang, P, Yang, XL, Dagan, A, Schimmel, P, Pozo, J, Razin, E, Shapiro, R, Bennett, SP, Wang, J, Ofir-Birin, Y, Guo, M, Kim, S, Song, J, Marshall, AG, Rachmin, I, Zhang, HM	Mol Cell	2013
22647378	The tumor suppressor HINT1 regulates MITF and β-catenin transcriptional activity in melanoma cells Sioletic, S, Sgambato, A, Cittadini, A, Rettino, A, Ghosh, P, Genovese, G, Li, H	Cell Cycle	2012
19524539	LysRS serves as a key signaling molecule in the immune response by regulating gene expression Kemeny, DM, Yang, CM, Razin, E, Nechushtan, H, Han, JM, Kay, G, Kim, S, Yannay-Cohen, N, Carmi-Levy, I	Mol Cell	2009