Reactome | MAPK-dependent phosphorylation of KARS

MAPK-dependent phosphorylation of KARS

Stable Identifier

R-HSA-9825759

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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A link between protein translation levels and MITF signaling is suggested by the role of the Lys tRNA synthetase, KARS (also called LysRS), in regulating MITF transcription factor by modulating the interaction of MITF with its HINT1 repressor protein (reviewed in Goding and Arnheiter, 2019)
KARS is part of a cytosolic complex called the multisynthetase complex (MSC) consisting of an additional 8 other amino-acyl tRNA synthetases and three non-enzymatic proteins (Bandyopadhyay and Deutscher, 1971). Upon KIT stimulation in melanoma cells, the KARS component is phosphorylated in a MAPK-dependent fashion at serine 207 (Razin et al, 1999; Yannay-Cohen et al, 2008; Ofir-Birin et al, 2013). This releases the KARS homodimer from the MSC, increasing the rate at which it synthesizes P(1),P(4)-bis(5'-adenosyl) tetraphosphate(4-) (AP4A) and allowing interaction of the KARS homodimer with MITF (Zamecnik et al, 1966; Razin et al, 1999; Carmi-Levy et al, 2008; Yannay-Cohen et al, 2009). AP4A binds to the MITF repressor HINT1 and disrupts the MITF-HINT1 interaction, relieving repression and allowing activation of MITF-dependent targets (Lee et al, 2004; Carmi-Levy et al, 2008; Yannay-Cohen et al, 2008).

Literature References

PubMed ID	Title	Journal	Year
5338216	Enzymatic synthesis of diadenosine tetraphosphate and diadenosine triphosphate with a purified lysyl-sRNA synthetase Zamecnik, PC, Stephenson, ML, Janeway, CM, Randerath, K	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, Nechushtan, H, Figov, N, Razin, E	Immunity	2004
5572099	Complex of aminoacyl-transfer RNA synthetases Bandyopadhyay, AK, Deutscher, MP	J Mol Biol	1971
31123060	MITF-the first 25 years Goding, CR, Arnheiter, H	Genes Dev	2019
10567402	Suppression of microphthalmia transcriptional activity by its association with protein kinase C-interacting protein 1 in mast cells Razin, E, Zhang, ZC, Nechushtan, H, Frenkel, S, Lee, YN, Arudchandran, R, Rivera, J	J Biol Chem	1999
18644867	Diadenosine tetraphosphate hydrolase is part of the transcriptional regulation network in immunologically activated mast cells Carmi-Levy, I, Yannay-Cohen, N, Kay, G, Razin, E, Nechushtan, H	Mol Cell Biol	2008
23159739	Structural switch of lysyl-tRNA synthetase between translation and transcription Ofir-Birin, Y, Fang, P, Bennett, SP, Zhang, HM, Wang, J, Rachmin, I, Shapiro, R, Song, J, Dagan, A, Pozo, J, Kim, S, Marshall, AG, Schimmel, P, Yang, XL, Nechushtan, H, Razin, E, Guo, M	Mol Cell	2013
19524539	LysRS serves as a key signaling molecule in the immune response by regulating gene expression Yannay-Cohen, N, Carmi-Levy, I, Kay, G, Yang, CM, Han, JM, Kemeny, DM, Kim, S, Nechushtan, H, Razin, E	Mol Cell	2009