Thr180
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Home > Phosphorylation Site Page: > Thr180  -  P38A (rat)

Site Information
RHTDDEMtGyVATRW   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447970

In vivo Characterization
Methods used to characterize site in vivo:
electrophoretic mobility shift ( 27 ) , immunoprecipitation ( 16 ) , mass spectrometry ( 7 , 14 , 18 , 19 , 21 , 22 , 23 , 24 ) , mutation of modification site ( 1 , 2 , 20 , 27 ) , phospho-antibody ( 1 , 2 , 3 , 6 , 8 , 9 , 10 , 11 , 13 , 15 , 16 , 17 , 20 , 25 , 26 , 27 , 28 , 29 , 30 , 32 , 33 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ) , western blotting ( 1 , 2 , 3 , 6 , 8 , 9 , 10 , 11 , 13 , 15 , 16 , 17 , 20 , 25 , 26 , 27 , 28 , 30 , 32 , 35 , 36 , 37 , 40 , 42 , 43 , 45 , 46 )
Disease tissue studied:
adrenal cancer ( 18 , 19 , 21 , 22 , 23 , 24 , 27 , 45 ) , pheochromocytoma ( 18 , 19 , 21 , 22 , 23 , 24 , 27 , 45 ) , bone cancer ( 43 ) , brain cancer ( 16 , 20 ) , glioblastoma ( 16 ) , glioma ( 16 , 20 ) , ovarian cancer ( 16 )
Relevant cell line - cell type - tissue:
'brain, hippocampus' ( 30 ) , 'muscle, skeletal' ( 13 , 17 , 36 , 39 , 42 ) , 'muscle, smooth'-thoracic aorta ( 33 , 40 ) , 293 (epithelial) ( 27 , 31 ) , 293T (epithelial) ( 16 ) , adipose tissue ( 37 ) , blood ( 7 ) , brain ( 14 ) , C6 (glial) ( 20 ) , Fao (hepatic) ( 26 ) , GN4 (epithelial) ( 38 ) , granulosa ( 29 ) , H9c2 (myoblast) ( 10 ) , heart ( 3 , 7 ) , intestine ( 7 ) , liver ( 7 , 28 , 32 , 35 ) , lung ( 7 , 8 ) , mesangial ( 25 ) , mesangial-kidney ( 1 ) , muscle ( 7 ) , myocyte-heart ( 2 , 10 , 31 ) , OVCAR5 (ovarian) ( 16 ) , PC-12 (chromaffin) ( 18 , 19 , 21 , 22 , 23 , 24 , 27 , 44 , 45 , 46 ) , RBL-2H3 (basophil) ( 15 , 41 ) , retinal-retina ( 6 ) , SNB-19 (glial) ( 16 ) , spinal cord ( 9 ) , spleen ( 7 ) , stomach ( 7 ) , testis ( 7 ) , thymus ( 7 ) , UMR106 (bone cell) ( 43 ) , VSMC ( 11 )

Upstream Regulation
Regulatory protein:
DUSP6 (human) ( 31 ) , EEA1 (human) ( 11 ) , HMOX1 (rat) ( 10 ) , PKCA (rat) ( 11 ) , RAP2A (human) ( 30 )
Putative in vivo kinases:
MKK3 (human) ( 44 ) , MKK6 (human) ( 44 )
Treatments:
A23187 ( 41 ) , A304000 ( 17 ) , acadesine ( 29 ) , activin ( 44 ) , angiotensin_2 ( 11 ) , anisomycin ( 46 ) , antigenic stimulation ( 15 ) , arsenite ( 27 ) , aspirin ( 15 ) , benzodiazepinones ( 16 ) , berberine ( 13 ) , betacellulin ( 33 ) , BIX02188 ( 9 ) , BMP2 ( 44 ) , C5b-9 ( 1 ) , ciglitazone ( 38 ) , CORM-2 ( 10 ) , culturing_of_cells ( 28 ) , diabetes ( 3 , 6 ) , EGF ( 43 ) , ethyl_pyruvate ( 8 ) , etoposide ( 20 ) , gefitinib ( 38 ) , glutathione ( 27 ) , GRGDSP ( 35 ) , hemorrhage ( 32 ) , hypoxia ( 45 ) , IGF-1 ( 29 ) , insulin ( 17 , 31 , 35 ) , ischemia/reperfusion ( 28 ) , lithium ( 17 ) , LPS ( 8 ) , LY294002 ( 28 ) , mechanical stress ( 2 ) , muscle atrophy ( 39 , 42 ) , NAC ( 27 , 38 ) , nafenopin ( 38 ) , NGF ( 46 ) , PD153035 ( 38 ) , PD169316 ( 36 ) , PD184352 ( 34 ) , PD98059 ( 28 , 36 ) , phenylephrine ( 31 ) , PP2 ( 35 , 38 ) , PP3 ( 38 ) , PTH ( 43 ) , rosiglitazone ( 37 ) , SB202190 ( 28 , 29 ) , SB203580 ( 28 , 34 , 43 , 44 ) , serum ( 29 , 40 ) , siRNA ( 2 ) , sorbitol ( 34 ) , SP600125 ( 36 ) , sphingomyelinase ( 26 ) , TGF-beta ( 25 ) , TNF ( 36 ) , trauma ( 32 ) , troglitazone ( 38 ) , U0126 ( 38 ) , urofollitropin ( 29 ) , UV ( 34 ) , vanadate ( 28 ) , VEGF ( 28 )

Downstream Regulation
Effects of modification on P38A:
activity, induced ( 2 ) , enzymatic activity, induced ( 44 )
Effects of modification on biological processes:
apoptosis, induced ( 1 ) , cell growth, altered ( 44 )

References 

1

Zhu G, et al. (2017) Sublytic C5b-9 Induces Glomerular Mesangial Cell Apoptosis through the Cascade Pathway of MEKK2-p38 MAPK-IRF-1-TRADD-Caspase 8 in Rat Thy-1 Nephritis. J Immunol 198, 1104-1118
28039298   Curated Info

2

Niu A, Wang B, Li YP (2015) TNF╬▒ shedding in mechanically stressed cardiomyocytes is mediated by Src activation of TACE. J Cell Biochem 116, 559-65
25371038   Curated Info

3

Reddy VS, Kumar ChU, Raghu G, Reddy GB (2014) Expression and induction of small heat shock proteins in rat heart under chronic hyperglycemic conditions. Arch Biochem Biophys 558, 1-9
24950024   Curated Info

4

Miranda CA, Lee JW, Chou CL, Knepper MA (2014) Tolvaptan as a tool in renal physiology. Am J Physiol Renal Physiol 306, F359-66
24305472   Curated Info

5

Jang JY, et al. (2014) Neuroprotective effects of a novel single compound 1-methoxyoctadecan-1-ol isolated from uncaria sinensis in primary cortical neurons and a photothrombotic ischemia model. PLoS One 9, e85322
24416390   Curated Info

6

Reddy VS, et al. (2013) Response of small heat shock proteins in diabetic rat retina. Invest Ophthalmol Vis Sci 54, 7674-82
24159092   Curated Info

7

Lundby A, et al. (2012) Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues. Nat Commun 3, 876
22673903   Curated Info

8

Kung CW, et al. (2011) Ethyl pyruvate reduces acute lung injury via regulation of iNOS and HO-1 expression in endotoxemic rats. J Surg Res 167, e323-31
21324485   Curated Info

9

Wang CG, et al. (2011) Activation of the spinal extracellular signal-regulated kinase 5 signaling pathway contributes to morphine physical dependence in rats. Neurosci Lett 494, 38-43
21356274   Curated Info

10

Lin HH, Lai SC, Chau LY (2011) Heme oxygenase-1/carbon monoxide induces vascular endothelial growth factor expression via p38 kinase-dependent activation of Sp1. J Biol Chem 286, 3829-38
21115498   Curated Info

11

Nazarewicz RR, et al. (2011) Early endosomal antigen 1 (EEA1) is an obligate scaffold for angiotensin II-induced, PKC-alpha-dependent Akt activation in endosomes. J Biol Chem 286, 2886-95
21097843   Curated Info

12

Zhou L, Too HP (2011) Mitochondrial localized STAT3 is involved in NGF induced neurite outgrowth. PLoS One 6, e21680
21738764   Curated Info

13

Ma X, et al. (2010) Berberine-induced activation of 5'-adenosine monophosphate-activated protein kinase and glucose transport in rat skeletal muscles. Metabolism 59, 1619-27
20423742   Curated Info

14

Hu Y (2010) CST Curation Set: 8921; Year: 2010; Biosample/Treatment: tissue, brain/ischemia; 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

15

Togo K, et al. (2009) Aspirin and salicylates modulate IgE-mediated leukotriene secretion in mast cells through a dihydropyridine receptor-mediated Ca(2+) influx. Clin Immunol 131, 145-56
19144570   Curated Info

16

Kim I, et al. (2009) Chemical biology investigation of cell death pathways activated by endoplasmic reticulum stress reveals cytoprotective modulators of ASK1. J Biol Chem 284, 1593-603
19004820   Curated Info

17

Macko AR, Beneze AN, Teachey MK, Henriksen EJ (2008) Roles of insulin signalling and p38 MAPK in the activation by lithium of glucose transport in insulin-resistant rat skeletal muscle. Arch Physiol Biochem 114, 331-9
19023684   Curated Info

18

Stokes M (2008) CST Curation Set: 5265; Year: 2008; Biosample/Treatment: cell line, PC-12/PACAP; Disease: pheochromocytoma; 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

19

Stokes M (2008) CST Curation Set: 5266; Year: 2008; Biosample/Treatment: cell line, PC-12/PACAP; Disease: pheochromocytoma; 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

Lomonaco SL, et al. (2008) Phosphorylation of protein kinase Cdelta on distinct tyrosine residues induces sustained activation of Erk1/2 via down-regulation of MKP-1: role in the apoptotic effect of etoposide. J Biol Chem 283, 17731-9
18434324   Curated Info

21

Stokes M (2008) CST Curation Set: 4008; Year: 2008; Biosample/Treatment: cell line, PC-12/untreated; Disease: pheochromocytoma; 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

Stokes M (2008) CST Curation Set: 4009; Year: 2008; Biosample/Treatment: cell line, PC-12/EGF; Disease: pheochromocytoma; 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

Stokes M (2008) CST Curation Set: 4012; Year: 2008; Biosample/Treatment: cell line, PC-12/untreated; Disease: pheochromocytoma; 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

Stokes M (2008) CST Curation Set: 4013; Year: 2008; Biosample/Treatment: cell line, PC-12/PACAP; Disease: pheochromocytoma; 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

Kim SM, et al. (2007) TGF-beta1-induced PINCH-1-ILK-alpha-parvin complex formation regulates mesangial cell proliferation and hypertrophy. Exp Mol Med 39, 514-23
17934340   Curated Info

26

Herschkovitz A, et al. (2007) Common inhibitory serine sites phosphorylated by IRS-1 kinases, triggered by insulin and inducers of insulin resistance. J Biol Chem 282, 18018-27
17446166   Curated Info

27

Cai B, et al. (2006) p38 MAP kinase mediates apoptosis through phosphorylation of BimEL at Ser-65. J Biol Chem 281, 25215-22
16818494   Curated Info

28

Ohi N, et al. (2006) Maintenance of Bad phosphorylation prevents apoptosis of rat hepatic sinusoidal endothelial cells in vitro and in vivo. Am J Pathol 168, 1097-106
16565486   Curated Info

29

Tosca L, et al. (2005) Adenosine 5'-monophosphate-activated protein kinase regulates progesterone secretion in rat granulosa cells. Endocrinology 146, 4500-13
16020477   Curated Info

30

Zhu Y, et al. (2005) Rap2-JNK removes synaptic AMPA receptors during depotentiation. Neuron 46, 905-16
15953419   Curated Info

31

Rolfe M, McLeod LE, Pratt PF, Proud CG (2005) Activation of protein synthesis in cardiomyocytes by the hypertrophic agent phenylephrine requires the activation of ERK and involves phosphorylation of tuberous sclerosis complex 2 (TSC2). Biochem J 388, 973-84
15757502   Curated Info

32

Ma Y, et al. (2004) Mechanisms of hemorrhage-induced hepatic insulin resistance: role of tumor necrosis factor-alpha. Endocrinology 145, 5168-76
15297437   Curated Info

33

Mifune M, et al. (2004) Signal transduction of betacellulin in growth and migration of vascular smooth muscle cells. Am J Physiol Cell Physiol 287, C807-13
15163624   Curated Info

34

Sabio G, et al. (2004) Stress- and mitogen-induced phosphorylation of the synapse-associated protein SAP90/PSD-95 by activation of SAPK3/p38gamma and ERK1/ERK2. Biochem J 380, 19-30
14741046   Curated Info

35

Schliess F, et al. (2004) Involvement of integrins and Src in insulin signaling toward autophagic proteolysis in rat liver. J Biol Chem 279, 21294-301
14985360   Curated Info

36

de Alvaro C, Teruel T, Hernandez R, Lorenzo M (2004) Tumor necrosis factor alpha produces insulin resistance in skeletal muscle by activation of inhibitor kappaB kinase in a p38 MAPK-dependent manner. J Biol Chem 279, 17070-8
14764603   Curated Info

37

Jiang G, et al. (2004) Rosiglitazone, an agonist of peroxisome-proliferator-activated receptor gamma (PPARgamma), decreases inhibitory serine phosphorylation of IRS1 in vitro and in vivo. Biochem J 377, 339-46
14556646   Curated Info

38

Gardner OS, et al. (2003) Dependence of peroxisome proliferator-activated receptor ligand-induced mitogen-activated protein kinase signaling on epidermal growth factor receptor transactivation. J Biol Chem 278, 46261-9
12966092   Curated Info

39

Hilder TL, et al. (2003) Phosphorylation of insulin receptor substrate-1 serine 307 correlates with JNK activity in atrophic skeletal muscle. FEBS Lett 553, 63-7
14550547   Curated Info

40

Haider UG, et al. (2003) Resveratrol increases serine15-phosphorylated but transcriptionally impaired p53 and induces a reversible DNA replication block in serum-activated vascular smooth muscle cells. Mol Pharmacol 63, 925-32
12644594   Curated Info

41

Sakamoto H, Tosaki T, Nakagawa Y (2002) Overexpression of phospholipid hydroperoxide glutathione peroxidase modulates acetyl-CoA, 1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase activity. J Biol Chem 277, 50431-8
12397078   Curated Info

42

Kato K, et al. (2002) Innervation-dependent phosphorylation and accumulation of alphaB-crystallin and Hsp27 as insoluble complexes in disused muscle. FASEB J 16, 1432-4
12205038   Curated Info

43

Swarthout JT, et al. (2002) Induction of transcriptional activity of the cyclic adenosine monophosphate response element binding protein by parathyroid hormone and epidermal growth factor in osteoblastic cells. J Bone Miner Res 17, 1401-7
12162494   Curated Info

44

Iwasaki S, et al. (1999) Specific activation of the p38 mitogen-activated protein kinase signaling pathway and induction of neurite outgrowth in PC12 cells by bone morphogenetic protein-2. J Biol Chem 274, 26503-10
10473611   Curated Info

45

Conrad PW, et al. (1999) Selective activation of p38alpha and p38gamma by hypoxia. Role in regulation of cyclin D1 by hypoxia in PC12 cells. J Biol Chem 274, 23570-6
10438538   Curated Info

46

Xing J, et al. (1998) Nerve growth factor activates extracellular signal-regulated kinase and p38 mitogen-activated protein kinase pathways to stimulate CREB serine 133 phosphorylation. Mol Cell Biol 18, 1946-55
9528766   Curated Info