TABLE 2

Phosphorylation sites in human translation factors and associated proteins, regulatory kinases, and functional consequences of the phosphorylationa

ProteinPhosphorylation site(s)b (reference) [main kinase(s)]Biological function(s) (reference[s])
4E-BP1Thr37 (317), Thr46 (317) [mTORC1 (117), GSK3β (126)]Priming sites (118, 119, 116)
Ser65 (317) [mTORC1 (117)], Thr70 (317) [mTORC1?/CDK1?]Dissociation from eIF4E (118, 119, 116)
Ser83 (129) [CDK1?], Ser85 (318) [?], Ser94 (319) [ATM?], Ser101 (320) [?], Ser112 (321) [CK2A1 (320)]Unknown
4E-BP2Thr37 (322), Thr46 (322) [mTORC1]Priming sites (by analogy with 4E-BP1)
Ser65 [mTORC1], Thr70 [mTORC1?/CDK1?]Dissociation from eIF4E (by analogy with 4E-BP1)
eIF4ESer209 (243) [MNK1/2 (245)]Unknown (244, 245), increases oncogenic activity and promotes translation of a subset of mRNAs (e.g., Mcl-1, MMPs, CCLs) (252)
eIF4GISer1185 [PKCα (323), TBK1? (324)]Modulates MNK binding (323)
Ser1106, Ser1147, Ser1194 [mTORC1] (184)Stimulation of translation of mRNAs containing uORFs (227) (?)
Ser896 [Pak2] (310)Inhibition of cap-dependent translation (310)
Ser1231 (325) [CDK1?]Inhibition of eIF4A/mRNA binding? (325)
eIF2αSer52 (326) [HRI, PKR, GCN2, PERK (reviewed in reference 4)]Stabilizes the eIF2/GDP/eIF2B complex, thus preventing recycling of eIF2 (reviewed in reference 4)
eIF2βS2, S67 [CK2 (327), mTORC1? (232)]Stimulates translation and proliferation (327); stimulates eIF2α dephosphorylation (232)
rpS6Ser235 (328) and Ser236 [S6K1/2, RSK (147)], Ser240, Ser244, and Ser247 [S6K1/2]Unknown (329, 330, 122, 147), global translation rates increased in MEFs expressing a nonphosphorylatable form of rpS6 (148)
PDCD4Ser67 [S6K1/2, AKT (163, 165)], Ser71 [?], Ser76 [RSK (331, 164)], Ser94 [?], Ser457 [S6K1/2, AKT (163, 165), RSK (164), PLK1? (332)]Degradation by the ubiquitin-proteasome system and subsequent activation of eIF4A (163, 164, 165)
eIF4BSer406 (172) [?], Ser422 [S6K1/2 (170), AKT (172), RSK (171)], Ser422 [MELK? (333)]Increases binding to eIF3 (173, 171), affects translation and proliferation (170)
eIF4HTyr12 (334), Tyr45 (334), Tyr101 (334), Ser193 (334) [?]Unknown
eIF2BεSer540 [GSK3] (335)Inhibits recycling of eIF2 (335)
Ser544 [DYRK] (336)Priming site for GSK3 (336)
Ser717/718 [CK2] (337)Facilitates eIF2 binding (337)
eIF3Subunit? [S6K1/2 (175)]Paip1-eIF3 interaction (175)
eIF3b: Ser83 (338), Ser85 (338), Ser125 (338) [?]Unknown
eIF3c: Ser39 (339), Ser166 (338), Thr524 (338), Ser909 (340) [?]Unknown
eIF3f: Ser46, Thr119 [CDK11] (341, 311)Regulation of protein synthesis and apoptosis (341, 311)
eIF3g: Thr41 (175), Ser42 (175) [?]Unknown
eIF3h: Ser183 (342) [?]Increased oncogenic activity (342)
eIF3i: Tyr445 (334) [?]Unknown
eIF1Tyr30 (334) [?]Unknown
Tyr72 (343) [?]Stimulation of mRNA translation (343)
eIF5Ser389, Ser390 [CK2] (344)Promotes cell cycle progression (344)
eIF5BSer107 (338), Ser113 (338), S135 (338), S137 (340), S164 (338), S182 (338), S183 (340), S186 (338), S190 (338), S214 (345), S1168 (338) [?]Unknown
eIF6Ser174/175 [CK1] (346)Nucleocytoplasmic shuttling (346)
Ser235 [PKCβII] (347)Dissociation of eIF6 from the 60S, 80S assembly (347)
eEF1A1Thr432 [PKCδ] (348)Activation (?) (348)
Ser21 (349) [BRAF?]Apoptosis (349)
Ser300 [TβR-I] (350)Inhibition of mRNA translation (350)
eEF1A2Ser205, Ser358 [JNK (351)]Degradation of newly synthesized polypeptides (351)
eEF2Thr56 [eEF2K] (352)Inhibits binding to the ribosome (353)
eEF2KSer78 (157) [mTOR?]Inhibits CaM binding (157)
Ser359 (155) [SAPK/p38δ?]Inhibition (?) (155)
Ser366 [S6K1, RSK] (150)Inhibition (150)
Ser398 [AMPK] (354)Activation (354)
Ser500 [PKA] (355)Induces Ca2+-independent activity (355)
  • a This table includes selected phosphoacceptor sites identified in large-scale mass spectrometry-based experiments which await functional characterization (e.g., eIF5B; unknown kinase/function is indicated by a question mark), as well as phosphorylation sites with established role in translational control (e.g., 4E-BPs and eIF2α). Further information on the as-of-yet functionally noncharacterized phosphorylated residues of the components of the translational apparatus can be found in the PhosphoSitePlus (www.phosphosite.org) or UniProt (www.uniprot.org) database. In the case of eIF4G1, the phosphorylation sites indicated are corrected from the published article (Ser1108, Ser1148, and Ser1192). Abbreviations: CDK, cyclin-dependent kinase; PKC, protein kinase C; Pak2, p21-activated kinase 2; HRI, heme-regulated eIF2α kinase; PKR, double-stranded-RNA-activated eIF2α kinase; GCN2, general control nonrepressed eIF2α kinase; PERK, double-stranded-RNA-activated protein kinase-like ER kinase; DYRK, dual-specificity tyrosine phosphorylation-regulated kinase; CK2, protein kinase CK2 (formerly known as casein kinase II); TβR-I, transforming growth factor β1 (TGF-β1) receptor; eEF2K, eukaryotic translation elongation factor 2 kinase; PKA, protein kinase A; SAPK, stress-activated protein kinase; TBK1, TANK-binding kinase 1, PLK1, polo-like kinase 1, MELK, maternal embryonic leucine zipper kinase; Paip1, polyadenylate-binding protein-interacting protein 1. Additional abbreviations are provided in the text.

  • b Amino acid numbering is based on human proteins.