Tyr42

Site Information
DsMkDEEyEQMVkEL SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 448737
Associated spectra: 2 CST

In vivo Characterization
Methods used to characterize site in vivo:	electrophoretic mobility shift ( 35 , 39 ) , mass spectrometry ( 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 31 , 32 ) , mutation of modification site ( 30 , 33 , 34 , 36 , 37 , 38 , 39 , 41 , 42 ) , phospho-antibody ( 13 , 29 , 30 , 33 , 34 , 35 , 38 , 41 ) , western blotting ( 13 , 29 , 30 , 34 , 42 )
Disease tissue studied:	bone cancer ( 13 ) , colorectal cancer ( 29 ) , colorectal carcinoma ( 29 ) , gastric cancer ( 18 ) , gastric carcinoma ( 18 ) , lung cancer ( 29 , 30 ) , non-small cell lung cancer ( 29 , 30 ) , non-small cell squamous cell lung carcinoma ( 29 ) , lymphoma ( 37 , 38 ) , T cell lymphoma ( 37 )
Relevant cell line - cell type - tissue:	A293 ('renal, embryonic') ( 30 ) , A549 (pulmonary) ( 29 ) , COS (fibroblast) [Src (human)] ( 39 ) , EL-4 (T lymphocyte) ( 37 ) , HCT116 (intestinal) ( 29 ) , HeLa (cervical) ( 34 ) , Huh7 (hepatic) ( 33 ) , JCaM-1 (T lymphocyte) ( 35 ) , JRK 154.6 (T lymphocyte) ( 35 ) , Jurkat (T lymphocyte) ( 2 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 14 , 15 , 16 , 17 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 32 , 35 , 41 , 42 ) , MKN-45 (gastric) ( 18 ) , NCI-H1299 (pulmonary) ( 29 , 30 ) , NCI-H1650 (pulmonary) ( 29 ) , NCI-H1703 (squamous) ( 29 ) , NCI-H23 (pulmonary) ( 29 ) , NCI-H460 (pulmonary) ( 29 ) , P116 (T lymphocyte) ( 35 ) , PC-12 (chromaffin) ( 36 ) , U-937 (myeloid) ( 38 ) , U2OS (bone cell) ( 13 )

Upstream Regulation
Regulatory protein:	Bcr (human) ( 1 ) , LKB1 (human) ( 29 )
Putative in vivo kinases:	Lck (human) ( 41 ) , Src iso1 (mouse) ( 39 )
Kinases, in vitro:	INSR (human) ( 41 ) , Lck (human) ( 41 )
Treatments:	EGF ( 30 ) , H2O2 ( 13 , 35 , 37 ) , hypoxia ( 13 ) , hypoxia/reoxygenation ( 34 , 41 ) , piceatannol ( 35 ) , PP1 ( 35 ) , siRNA ( 29 ) , TNF ( 34 , 39 ) , UV ( 34 ) , vanadate ( 13 , 34 , 35 , 38 , 41 )

Downstream Regulation
Effects of modification on IkB-alpha:	activity, induced ( 30 , 37 ) , molecular association, regulation ( 41 ) , protein degradation ( 33 , 37 )
Effects of modification on biological processes:	apoptosis, inhibited ( 34 ) , transcription, altered ( 36 , 37 ) , transcription, induced ( 34 )
Inhibit interaction with:	NFkB-p65 (human) ( 41 )

References
1	Pontoriero M, et al. (2019) Activation of NF-κB in B cell receptor signaling through Bruton's tyrosine kinase-dependent phosphorylation of IκB-α. J Mol Med (Berl) 97 30887112 Curated Info
2	Zhou J (2012) CST Curation Set: 14432; Year: 2012; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY] Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine (P-Tyr-1000) Rabbit mAb Cat#: 8954, Phospho-Tyrosine Rabbit mAb (p-Tyr-1000) Immunoaffinity Beads Cat#: 8876 Curated Info
3	Stokes MP, et al. (2012) PTMScan Direct: Identification and Quantification of Peptides from Critical Signaling Proteins by Immunoaffinity Enrichment Coupled with LC-MS/MS. Mol Cell Proteomics 11, 187-201 22322096 Curated Info
4	Zhou J (2012) CST Curation Set: 12609; Year: 2012; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Curated Info
5	Zhou J (2012) CST Curation Set: 12612; Year: 2012; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Curated Info
6	Zhou J (2011) CST Curation Set: 12495; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
7	Zhou J (2011) CST Curation Set: 12496; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
8	Zhou J (2011) CST Curation Set: 12497; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
9	Zhou J (2011) CST Curation Set: 12314; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY] Curated Info
10	Zhou J (2011) CST Curation Set: 12026; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY(YXXM) Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Tyr) p85 PI3K Binding Motif Antibody Cat#: 3821 Curated Info
11	Zhou J (2011) CST Curation Set: 12029; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY(YXXM) Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Tyr) p85 PI3K Binding Motif Antibody Cat#: 3821 Curated Info
12	Possemato A (2011) CST Curation Set: 11629; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
13	Culver C, et al. (2010) Mechanism of Hypoxia-Induced NF-{kappa}B. Mol Cell Biol 30, 4901-21 20696840 Curated Info
14	Possemato A (2010) CST Curation Set: 10537; Year: 2010; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
15	Tucker M (2010) CST Curation Set: 10319; Year: 2010; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
16	Ren H (2010) CST Curation Set: 10170; Year: 2010; Biosample/Treatment: cell line, Jurkat/pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411 Curated Info
17	Possemato A (2010) CST Curation Set: 9436; Year: 2010; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P Curated Info
18	Moritz A (2010) CST Curation Set: 9234; Year: 2010; Biosample/Treatment: cell line, MKN-45/calyculin_A & pervanadate; Disease: gastric carcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY]) Curated Info
19	Possemato A (2009) CST Curation Set: 8804; Year: 2009; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
20	Moritz A (2009) CST Curation Set: 8213; Year: 2009; Biosample/Treatment: cell line, Jurkat/pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
21	Possemato A (2009) CST Curation Set: 8188; Year: 2009; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
22	Possemato A (2009) CST Curation Set: 7996; Year: 2009; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
23	Possemato A (2009) CST Curation Set: 7997; Year: 2009; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
24	Possemato A (2009) CST Curation Set: 7994; Year: 2009; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
25	Possemato A (2009) CST Curation Set: 7995; Year: 2009; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
26	Rikova K (2009) CST Curation Set: 7720; Year: 2009; Biosample/Treatment: cell line, Jurkat K/pervanadate; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
27	Rikova K (2009) CST Curation Set: 7721; Year: 2009; Biosample/Treatment: cell line, Jurkat A/pervanadate; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
28	Possemato A (2009) CST Curation Set: 7999; Year: 2009; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
29	Zhong D, et al. (2008) LKB1 is necessary for Akt-mediated phosphorylation of proapoptotic proteins. Cancer Res 68, 7270-7 18794113 Curated Info
30	Sethi G, Ahn KS, Chaturvedi MM, Aggarwal BB (2007) Epidermal growth factor (EGF) activates nuclear factor-kappaB through IkappaBalpha kinase-independent but EGF receptor-kinase dependent tyrosine 42 phosphorylation of IkappaBalpha. Oncogene 26, 7324-32 17533369 Curated Info
31	Cherry J (2007) CST Curation Set: 2525; Year: 2007; Biosample/Treatment: cell line, Nomo-1/SAHA 3h; Disease: acute myelogenous leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
32	Possemato A (2004) CST Curation Set: 7998; Year: 2009; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
33	Waris G, et al. (2003) Hepatitis C virus NS5A and subgenomic replicon activate NF-kappaB via tyrosine phosphorylation of IkappaBalpha and its degradation by calpain protease. J Biol Chem 278, 40778-87 12909638 Curated Info
34	Fan C, Yang J, Engelhardt JF (2002) Temporal pattern of NFkappaB activation influences apoptotic cell fate in a stimuli-dependent fashion. J Cell Sci 115, 4843-53 12432072 Curated Info
35	Livolsi A, et al. (2001) Tyrosine phosphorylation-dependent activation of NF-kappa B. Requirement for p56 LCK and ZAP-70 protein tyrosine kinases. Eur J Biochem 268, 1508-15 11231305 Curated Info
36	Bui NT, Livolsi A, Peyron JF, Prehn JH (2001) Activation of nuclear factor kappaB and Bcl-x survival gene expression by nerve growth factor requires tyrosine phosphorylation of IkappaBalpha. J Cell Biol 152, 753-64 11266466 Curated Info
37	Schoonbroodt S, et al. (2000) Crucial role of the amino-terminal tyrosine residue 42 and the carboxyl-terminal PEST domain of I kappa B alpha in NF-kappa B activation by an oxidative stress. J Immunol 164, 4292-300 10754328 Curated Info
38	Mukhopadhyay A, Manna SK, Aggarwal BB (2000) Pervanadate-induced nuclear factor-kappaB activation requires tyrosine phosphorylation and degradation of IkappaBalpha. Comparison with tumor necrosis factor-alpha. J Biol Chem 275, 8549-55 10722693 Curated Info
39	Abu-Amer Y, et al. (1998) Tumor necrosis factor-alpha activation of nuclear transcription factor-kappaB in marrow macrophages is mediated by c-Src tyrosine phosphorylation of Ikappa Balpha. J Biol Chem 273, 29417-23 9792645 Curated Info
40	DiDonato JA, et al. (1997) A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB. Nature 388, 548-54 9252186 Curated Info
41	Imbert V, et al. (1996) Tyrosine phosphorylation of I kappa B-alpha activates NF-kappa B without proteolytic degradation of I kappa B-alpha. Cell 86, 787-98 8797825 Curated Info
42	Brockman JA, et al. (1995) Coupling of a signal response domain in I kappa B alpha to multiple pathways for NF-kappa B activation. Mol Cell Biol 15, 2809-18 7739562 Curated Info