Thr423
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Home > Phosphorylation Site Page: > Thr423  -  PAK1 (human)

Site Information
PEQSkRstMVGtPYW   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448177
Available spectra:  1 CST

In vivo Characterization
Methods used to characterize site in vivo:
immunoprecipitation ( 7 , 9 ) , mass spectrometry ( 3 , 10 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 25 ) , microscopy-colocalization with upstream kinase ( 31 ) , mutation of modification site ( 2 , 3 , 4 , 9 , 27 ) , phospho-antibody ( 2 , 3 , 4 , 6 , 7 , 9 , 11 , 12 , 13 , 14 , 15 , 24 , 27 , 28 , 30 , 31 , 33 ) , western blotting ( 1 , 2 , 3 , 4 , 6 , 7 , 9 , 11 , 12 , 13 , 14 , 15 , 24 , 27 , 28 , 31 , 33 )
Disease tissue studied:
breast cancer ( 2 , 4 , 11 ) , colorectal cancer ( 7 , 9 ) , colorectal carcinoma ( 7 , 9 ) , lung cancer ( 1 , 6 , 10 , 13 ) , non-small cell lung cancer ( 1 , 6 , 13 ) , non-small cell lung adenocarcinoma ( 1 , 10 ) , non-small cell squamous cell lung carcinoma ( 1 , 10 ) , ovarian cancer ( 14 ) , prostate cancer ( 7 ) , rhabdomyosarcoma ( 6 )
Relevant cell line - cell type - tissue:

Upstream Regulation
Regulatory protein:
CDC42 iso1 (human) ( 15 , 33 ) , IL24 (human) ( 5 ) , NDRG1 (human) ( 7 ) , PKG1 iso2 (human) ( 28 ) , PTP-PEST (human) ( 2 ) , RAC1 (human) ( 28 , 33 ) , RHOU (human) ( 13 )
Kinases, in vitro:
PAK1 (human) ( 26 , 32 , 34 ) , PDK1 (human) ( 32 )
Treatments:
5-HT ( 27 ) , AG1478 ( 33 ) , anti-CD3 ( 25 ) , Auranofin ( 1 ) , blood pressure ( 12 ) , fluid_shear_stress ( 3 ) , GNF2 ( 3 ) , heregulin ( 11 ) , HGF ( 14 ) , imatinib ( 3 ) , IPA-3 ( 1 , 9 , 11 ) , LY294002 ( 33 ) , osimertinib ( 1 ) , OTSSP167 ( 1 ) , PDGF ( 33 ) , PP1 ( 33 ) , PRL ( 4 ) , serum ( 31 ) , thymoquinone ( 9 ) , TNF ( 24 ) , wounding ( 33 )

Downstream Regulation
Effects of modification on PAK1:
activity, induced ( 8 ) , enzymatic activity, induced ( 4 , 15 , 26 , 34 ) , enzymatic activity, inhibited ( 9 ) , molecular association, regulation ( 2 , 15 ) , phosphorylation ( 2 ) , protein conformation ( 15 , 29 )
Effects of modification on biological processes:
apoptosis, induced ( 9 ) , carcinogenesis, induced ( 1 ) , cell growth, induced ( 1 ) , cell motility, induced ( 3 ) , signaling pathway regulation ( 9 )
Induce interaction with:
CDC42 iso1 (human) ( 15 , 34 ) , PAK1 (human) ( 2 )

Disease / Diagnostics Relevance
Relevant diseases:
non-small cell lung cancer ( 1 , 6 ) , ovarian cancer ( 14 )

References 

1

Ito M, et al. (2019) Targeting PKCι-PAK1 signaling pathways in EGFR and KRAS mutant adenocarcinoma and lung squamous cell carcinoma. Cell Commun Signal 17, 137
31660987   Curated Info

2

Li H, et al. (2018) Switching of the substrate specificity of protein tyrosine phosphatase N12 by cyclin-dependent kinase 2 phosphorylation orchestrating 2 oncogenic pathways. FASEB J 32, 73-82
28842430   Curated Info

3

Tong H, et al. (2017) c-Abl tyrosine kinase regulates neutrophil crawling behavior under fluid shear stress via Rac/PAK/LIMK/cofilin signaling axis. J Cell Biochem
29058761   Curated Info

4

Oladimeji P, Diakonova M (2016) PAK1 translocates into nucleus in response to prolactin but not to estrogen. Biochem Biophys Res Commun 473, 206-11
27003261   Curated Info

5

Panneerselvam J, et al. (2015) Phosphorylation of interleukin (IL)-24 is required for mediating its anti-cancer activity. Oncotarget 6, 16271-86
26009991   Curated Info

6

Mortazavi F, et al. (2015) Significance of KRAS/PAK1/Crk pathway in non-small cell lung cancer oncogenesis. BMC Cancer 15, 381
25956913   Curated Info

7

Liu W, et al. (2015) The proto-oncogene c-Src and its downstream signaling pathways are inhibited by the metastasis suppressor, NDRG1. Oncotarget 6, 8851-74
25860930   Curated Info

8

Hammer A, Oladimeji P, De Las Casas LE, Diakonova M (2015) Phosphorylation of tyrosine 285 of PAK1 facilitates βPIX/GIT1 binding and adhesion turnover. FASEB J 29, 943-59
25466889   Curated Info

9

El-Baba C, et al. (2014) Thymoquinone-induced conformational changes of PAK1 interrupt prosurvival MEK-ERK signaling in colorectal cancer. Mol Cancer 13, 201
25174975   Curated Info

10

Rikova K, Hall B (2013) CST Curation Set: 20739, 21166, 30167, 30168, 30169; Year: 2013; Biosample/Treatment: cell line, H2342, H2073, Lou-NH91, HCC15, H1703; Disease: -; TMT: Y; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY, p[ST], RXXp[ST], pSQ, p[ST]QG, LXRXXp[ST], p[ST]P
Curated Info

11

Ghosh A, Awasthi S, Peterson JR, Hamburger AW (2013) Regulation of tamoxifen sensitivity by a PAK1-EBP1 signalling pathway in breast cancer. Br J Cancer 108, 557-63
23361053   Curated Info

12

Cheng G, et al. (2010) Basis for MAP4 Dephosphorylation-related Microtubule Network Densification in Pressure Overload Cardiac Hypertrophy. J Biol Chem 285, 38125-40
20889984   Curated Info

13

Alan JK, et al. (2010) Regulation of the Rho family small GTPase Wrch-1/RhoU by C-terminal tyrosine phosphorylation requires Src. Mol Cell Biol 30, 4324-38
20547754   Curated Info

14

Siu MK, et al. (2010) Differential expression and phosphorylation of Pak1 and Pak2 in ovarian cancer: effects on prognosis and cell invasion. Int J Cancer 127, 21-31
19876919   Curated Info

15

Parrini MC, Camonis J, Matsuda M, de Gunzburg J (2009) Dissecting activation of the PAK1 kinase at protrusions in living cells. J Biol Chem 284, 24133-43
19574218   Curated Info

16

Zhou J (2009) CST Curation Set: 7600; Year: 2009; Biosample/Treatment: cell line, HeLa/untreated; Disease: cervical adenocarcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

17

Zhou J (2009) CST Curation Set: 7598; Year: 2009; Biosample/Treatment: cell line, HeLa/untreated; Disease: cervical adenocarcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

18

Zhou J (2009) CST Curation Set: 7597; Year: 2009; Biosample/Treatment: cell line, HeLa/untreated; Disease: cervical adenocarcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

19

Zhou J (2009) CST Curation Set: 7596; Year: 2009; Biosample/Treatment: cell line, HeLa/untreated; Disease: cervical adenocarcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

20

Zhou J (2009) CST Curation Set: 7595; Year: 2009; Biosample/Treatment: cell line, HeLa/untreated; Disease: cervical adenocarcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

21

Zhou J (2009) CST Curation Set: 7592; Year: 2009; Biosample/Treatment: cell line, HeLa/untreated; Disease: cervical adenocarcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

22

Zhou J (2009) CST Curation Set: 7594; Year: 2009; Biosample/Treatment: cell line, HeLa/untreated; Disease: cervical adenocarcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

23

Zhou J (2009) CST Curation Set: 7591; Year: 2009; Biosample/Treatment: cell line, HeLa/untreated; Disease: cervical adenocarcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

24

Zhou L, et al. (2009) Tumor necrosis factor-alpha induced expression of matrix metalloproteinase-9 through p21-activated kinase-1. BMC Immunol 10, 15
19298660   Curated Info

25

Mayya V, et al. (2009) Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal 2, ra46
19690332   Curated Info

26

Guo D, et al. (2007) A Rac-cGMP signaling pathway. Cell 128, 341-55
17254971   Curated Info

27

Li QF, et al. (2006) Critical role of vimentin phosphorylation at Ser-56 by p21-activated kinase in vimentin cytoskeleton signaling. J Biol Chem 281, 34716-24
16990256   Curated Info

28

Fryer BH, et al. (2006) cGMP-dependent protein kinase phosphorylates p21-activated kinase (Pak) 1, inhibiting Pak/Nck binding and stimulating Pak/vasodilator-stimulated phosphoprotein association. J Biol Chem 281, 11487-95
16490784   Curated Info

29

Lei M, Robinson MA, Harrison SC (2005) The active conformation of the PAK1 kinase domain. Structure 13, 769-78
15893667   Curated Info

30

Parsons M, et al. (2005) Spatially distinct binding of Cdc42 to PAK1 and N-WASP in breast carcinoma cells. Mol Cell Biol 25, 1680-95
15713627   Curated Info

31

Stockton RA, Schaefer E, Schwartz MA (2004) p21-activated kinase regulates endothelial permeability through modulation of contractility. J Biol Chem 279, 46621-30
15333633   Curated Info

32

King CC, et al. (2000) p21-activated kinase (PAK1) is phosphorylated and activated by 3-phosphoinositide-dependent kinase-1 (PDK1). J Biol Chem 275, 41201-9
10995762   Curated Info

33

Sells MA, Pfaff A, Chernoff J (2000) Temporal and spatial distribution of activated Pak1 in fibroblasts. J Cell Biol 151, 1449-58
11134074   Curated Info

34

Zenke FT, King CC, Bohl BP, Bokoch GM (1999) Identification of a central phosphorylation site in p21-activated kinase regulating autoinhibition and kinase activity. J Biol Chem 274, 32565-73
10551809   Curated Info