Thr508
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Home > Phosphorylation Site Page: > Thr508  -  LIMK1 (human)

Site Information
PDRKKRYtVVGNPYW   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447808

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 20 ) , immunoassay ( 11 ) , immunoprecipitation ( 4 , 7 ) , mass spectrometry ( 1 , 10 ) , mutation of modification site ( 1 , 3 , 14 , 18 , 19 , 20 ) , phospho-antibody ( 1 , 4 , 5 , 6 , 7 , 8 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ) , western blotting ( 1 , 4 , 5 , 6 , 7 , 8 , 11 , 12 , 13 , 14 , 15 , 16 , 17 )
Disease tissue studied:
bone cancer ( 5 ) , brain cancer ( 6 ) , Schwannoma ( 6 ) , breast cancer ( 7 , 8 , 11 , 14 ) , breast adenocarcinoma ( 7 ) , breast cancer, triple negative ( 7 ) , neuroblastoma ( 13 ) , prostate cancer ( 4 ) , cancer, squamous cell carcinoma ( 3 )
Relevant cell line - cell type - tissue:

Upstream Regulation
Regulatory protein:
LIMK1 (human) ( 16 ) , Merlin (mouse) ( 6 ) , NISCH (mouse) ( 14 ) , PAK1 (human) ( 14 ) , PRKD3 (human) ( 7 ) , PTEN (human) ( 8 ) , RAC1 (human) ( 5 ) , YB-1 (human) ( 11 )
Putative in vivo kinases:
AurA (human) ( 9 ) , PAK6 (mouse) ( 4 ) , ROCK1 (human) ( 20 )
Kinases, in vitro:
AurA (human) ( 9 ) , PAK1 (human) ( 21 ) , PAK4 (human) ( 2 ) , PAK6 (human) ( 4 ) , ROCK1 (human) ( 20 )
Treatments:
BI-D1870 ( 11 ) , CTGF ( 15 ) , estradiol ( 13 ) , fibronectin ( 5 ) , fluid_shear_stress ( 1 ) , GNF2 ( 1 ) , H1152 ( 17 ) , heat_shock ( 12 ) , imatinib ( 1 ) , interleukin-6-hydroxymethyl-chiro-inositol-2(R)-2-methyl-3-O-octadecylcarbonate ( 15 ) , LPA ( 20 ) , LY294002 ( 15 ) , miRNA ( 4 ) , RGDS ( 17 ) , serum ( 14 ) , tanespimycin ( 16 ) , thrombin ( 17 ) , Y27632 ( 17 , 20 )

Downstream Regulation
Effects of modification on LIMK1:
activity, induced ( 6 , 19 ) , enzymatic activity, induced ( 9 , 14 , 18 , 20 ) , molecular association, regulation ( 14 ) , phosphorylation ( 9 )
Effects of modification on biological processes:
cell cycle regulation ( 11 ) , cell motility, induced ( 1 )
Induce interaction with:
NISCH (mouse) ( 14 )

Disease / Diagnostics Relevance
Relevant diseases:
Schwannoma ( 6 )

References 

1

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

2

Hamill S, Lou HJ, Turk BE, Boggon TJ (2016) Structural Basis for Noncanonical Substrate Recognition of Cofilin/ADF Proteins by LIM Kinases. Mol Cell 62, 397-408
27153537   Curated Info

3

Martín-Villar E, et al. (2015) Podoplanin mediates ECM degradation by squamous carcinoma cells through control of invadopodia stability. Oncogene 34, 4531-44
25486435   Curated Info

4

Cai S, et al. (2015) Downregulation of microRNA-23a suppresses prostate cancer metastasis by targeting the PAK6-LIMK1 signaling pathway. Oncotarget 6, 3904-17
25714010   Curated Info

5

Pasapera AM, et al. (2015) Rac1-Dependent Phosphorylation and Focal Adhesion Recruitment of Myosin IIA Regulates Migration and Mechanosensing. Curr Biol 25, 175-86
25544611   Curated Info

6

Petrilli A, et al. (2014) LIM domain kinases as potential therapeutic targets for neurofibromatosis type 2. Oncogene 33, 3571-82
23934191   Curated Info

7

Döppler H, et al. (2014) Protein kinase d isoforms differentially modulate cofilin-driven directed cell migration. PLoS One 9, e98090
24840177   Curated Info

8

Vitolo MI, et al. (2013) Loss of PTEN induces microtentacles through PI3K-independent activation of cofilin. Oncogene 32, 2200-10
22689060   Curated Info

9

Ritchey L, Ottman R, Roumanos M, Chakrabarti R (2012) A functional cooperativity between Aurora A kinase and LIM kinase1: implication in the mitotic process. Cell Cycle 11, 296-309
22214762   Curated Info

10

Mulhern D (2011) CST Curation Set: 13106; 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

11

Davies AH, et al. (2011) YB-1 evokes susceptibility to cancer through cytokinesis failure, mitotic dysfunction and HER2 amplification. Oncogene 30, 3649-60
21423216   Curated Info

12

Simard JP, et al. (2011) Overexpression of HSP70 inhibits cofilin phosphorylation and promotes lymphocyte migration in heat-stressed cells. J Cell Sci 124, 2367-74
21693580   Curated Info

13

Yuen GS, McEwen BS, Akama KT (2011) LIM kinase mediates estrogen action on the actin depolymerization factor Cofilin. Brain Res 1379, 44-52
20696146   Curated Info

14

Ding Y, Milosavljevic T, Alahari SK (2008) Nischarin inhibits LIM kinase to regulate cofilin phosphorylation and cell invasion. Mol Cell Biol 28, 3742-56
18332102   Curated Info

15

Crean JK, et al. (2006) Connective tissue growth factor/CCN2 stimulates actin disassembly through Akt/protein kinase B-mediated phosphorylation and cytoplasmic translocation of p27(Kip-1). FASEB J 20, 1712-4
16790529   Curated Info

16

Li R, et al. (2006) Hsp90 increases LIM kinase activity by promoting its homo-dimerization. FASEB J 20, 1218-20
16641196   Curated Info

17

Pandey D, Goyal P, Bamburg JR, Siess W (2006) Regulation of LIM-kinase 1 and cofilin in thrombin-stimulated platelets. Blood 107, 575-83
16219803   Curated Info

18

Soosairajah J, et al. (2005) Interplay between components of a novel LIM kinase-slingshot phosphatase complex regulates cofilin. EMBO J 24, 473-86
15660133   Curated Info

19

Nishita M, Aizawa H, Mizuno K (2002) Stromal cell-derived factor 1alpha activates LIM kinase 1 and induces cofilin phosphorylation for T-cell chemotaxis. Mol Cell Biol 22, 774-83
11784854   Curated Info

20

Ohashi K, et al. (2000) Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at threonine 508 within the activation loop. J Biol Chem 275, 3577-82
10652353   Curated Info

21

Edwards DC, Sanders LC, Bokoch GM, Gill GN (1999) Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics. Nat Cell Biol 1, 253-9
10559936   Curated Info