Reactome | p-S207 KARS1 dimer synthesizes A(5')p4(5')A

p-S207 KARS1 dimer synthesizes A(5')p4(5')A

Stable Identifier

R-HSA-9825790

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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p-S207 KARS1 dimer synthesizes A(5')p4(5')A

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MAPK-dependent phosphorylation at serine 207 stimulates release of the KARS homodimer from the multisynthetase complex and stimulates its rate of synthesis of AP4A (P(1),P(4)-bis(5'-adenosyl) tetraphosphate(4-)) at the expense of tRNA aminoacylation (Zamecik et al, 1996; Ofir-BIrin et al, 2013; Yannay-Cohen et al, 2009). AP4A binds to the MITF repressor protein HINT1 and dissociates it from MITF, activating MITF-dependent signaling (Lee et al, 2004; Carmi-Levy et al, 2008; Yannay-Cohen et al, 2009). In this way, serine phosphorylation of the KARS homodimer promotes a change in function from a role in translation (through aminoacylation) to one in transcription (through increased MITF-dependent gene expression) (Yannay-Cohen et al, 2009; Ofir-Birin et al, 2013; reviewed in Goding and Arnheiter, 2019).

Literature References

PubMed ID	Title	Journal	Year
5338216	Enzymatic synthesis of diadenosine tetraphosphate and diadenosine triphosphate with a purified lysyl-sRNA synthetase Zamecnik, PC, Janeway, CM, Randerath, K, Stephenson, ML	Biochem Biophys Res Commun	1966
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
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