Integrin-linked kinase

Integrin-linked kinase
Rendering based on PDB 2KBX​.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2KBX​, 3F6Q​, 3IXE​, 3KMU​, 3KMW​, 3REP​, 4HI8​, 4HI9​
Identifiers
Symbols	ILK ; HEL-S-28; ILK-1; ILK-2; P59; p59ILK
External IDs	OMIM: 602366 MGI: 1195267 HomoloGene: 3318 ChEMBL: 5247 GeneCards: ILK Gene
EC number	2.7.11.1
Gene ontology Molecular function • protein serine/threonine kinase activity • signal transducer activity • integrin binding • protein binding • ATP binding • SH3 domain binding • protein kinase binding Cellular component • stress fiber • nucleoplasm • cytoplasm • cytosol • plasma membrane • cell-cell junction • focal adhesion • membrane • sarcomere • lamellipodium • cell junction • extracellular matrix • neuronal cell body • costamere • terminal bouton • dendritic shaft • protein complex Biological process • branching involved in ureteric bud morphogenesis • positive regulation of cell-matrix adhesion • outflow tract morphogenesis • protein phosphorylation • negative regulation of protein kinase activity • cell cycle arrest • cell-matrix adhesion • integrin-mediated signaling pathway • cell aging • cell proliferation • positive regulation of cell proliferation • negative regulation of cardiac muscle cell apoptotic process • fibroblast migration • negative regulation of smooth muscle cell migration • peptidyl-serine phosphorylation • nerve development • myelination in peripheral nervous system • positive regulation of cell migration • positive regulation of BMP signaling pathway • myelin assembly • regulation of actin cytoskeleton organization • cell junction assembly • substrate adhesion-dependent cell spreading • positive regulation of phosphorylation • extracellular fibril organization • positive regulation of MAP kinase activity • protein kinase B signaling • negative regulation of neuron apoptotic process • establishment or maintenance of epithelial cell apical/basal polarity • positive regulation of myoblast differentiation • positive regulation of osteoblast differentiation • positive regulation of axon extension • positive regulation of transcription, DNA-templated • negative regulation of smooth muscle cell proliferation • neuron projection morphogenesis • positive regulation of dendrite morphogenesis • protein heterooligomerization • positive regulation of protein kinase B signaling • platelet aggregation • positive regulation of canonical Wnt signaling pathway • negative regulation of neural precursor cell proliferation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3611	16202
Ensembl	ENSG00000166333	ENSMUSG00000030890
UniProt	Q13418	O55222
RefSeq (mRNA)	NM_001014794	NM_001161724
RefSeq (protein)	NP_001014794	NP_001155196
Location (UCSC)	Chr 11: 6.6 – 6.61 Mb	Chr 7: 105.74 – 105.74 Mb
PubMed search

Integrin-linked kinase (ILK) is a 59kDa protein originally identified while conducting a yeast-two hybrid screen with integrin β1 as the bait protein (Hannigan et al., 1996). Since its discovery, ILK has been associated with multiple cellular functions including cell migration, cell proliferation, cell-adhesions, and signal transduction.

Function

Transduction of extracellular matrix signals through integrins influences intracellular and extracellular functions, and appears to require interaction of integrin cytoplasmic domains with cellular proteins. Integrin-linked kinase (ILK), interacts with the cytoplasmic domain of beta-1 integrin. This gene was initially described to encode a serine/threonine protein kinase with 4 ankyrin-like repeats, which associates with the cytoplasmic domain of beta integrins and acts as a proximal receptor kinase regulating integrin-mediated signal transduction. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene.^[1] Recent results showed that ILK contains 5 ankyrin-like repeats, and that the C-terminal kinase domain is actually a pseudo-kinase with adaptor function.^[2][3][4]

In 2008, ILK was found to localize to the centrosome and regulate mitotic spindle organization.^[5]

Interactions

Integrin-linked kinase has been shown to interact with:

• ACP6,^[6]
• AKT1,^[7][8][9]
• ILKAP,^[10] and
• LIMS1,^[11][12]

References

1. "Entrez Gene: ILK integrin-linked kinase".
2. "Integrin-linked kinase is an adaptor with essential functions during mouse development.". NCBI. October 2009.
3. "The pseudoactive site of ILK is essential for its binding to alpha-Parvin and localization to focal adhesions". NCBI. December 2009.
4. "ILK: a pseudokinase in the center stage of cell-matrix adhesion and signaling". NCBI. October 2012.
5. Fielding AB, Dobreva I, McDonald PC, Foster LJ, Dedhar S (Feb 2008). "Integrin-linked kinase localizes to the centrosome and regulates mitotic spindle organization". The Journal of Cell Biology 180 (4): 681–9. doi:10.1083/jcb.200710074. PMC 2265580. PMID 18283114.
6. Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology 3: 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
7. Barry FA, Gibbins JM (Apr 2002). "Protein kinase B is regulated in platelets by the collagen receptor glycoprotein VI". The Journal of Biological Chemistry 277 (15): 12874–8. doi:10.1074/jbc.M200482200. PMID 11825911.
8. Delcommenne M, Tan C, Gray V, Rue L, Woodgett J, Dedhar S (Sep 1998). "Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase". Proceedings of the National Academy of Sciences of the United States of America 95 (19): 11211–6. doi:10.1073/pnas.95.19.11211. PMC 21621. PMID 9736715.
9. Persad S, Attwell S, Gray V, Mawji N, Deng JT, Leung D, Yan J, Sanghera J, Walsh MP, Dedhar S (Jul 2001). "Regulation of protein kinase B/Akt-serine 473 phosphorylation by integrin-linked kinase: critical roles for kinase activity and amino acids arginine 211 and serine 343". The Journal of Biological Chemistry 276 (29): 27462–9. doi:10.1074/jbc.M102940200. PMID 11313365.
10. Leung-Hagesteijn C, Mahendra A, Naruszewicz I, Hannigan GE (May 2001). "Modulation of integrin signal transduction by ILKAP, a protein phosphatase 2C associating with the integrin-linked kinase, ILK1". The EMBO Journal 20 (9): 2160–70. doi:10.1093/emboj/20.9.2160. PMC 125446. PMID 11331582.
11. Tu Y, Li F, Goicoechea S, Wu C (Mar 1999). "The LIM-only protein PINCH directly interacts with integrin-linked kinase and is recruited to integrin-rich sites in spreading cells". Molecular and Cellular Biology 19 (3): 2425–34. doi:10.1128/mcb.19.3.2425. PMC 84035. PMID 10022929.
12. Zhang Y, Chen K, Guo L, Wu C (Oct 2002). "Characterization of PINCH-2, a new focal adhesion protein that regulates the PINCH-1-ILK interaction, cell spreading, and migration". The Journal of Biological Chemistry 277 (41): 38328–38. doi:10.1074/jbc.M205576200. PMID 12167643.

Further reading

• Dedhar S (Apr 2000). "Cell-substrate interactions and signaling through ILK". Current Opinion in Cell Biology 12 (2): 250–6. doi:10.1016/S0955-0674(99)00083-6. PMID 10712922.
• Persad S, Dedhar S (Dec 2003). "The role of integrin-linked kinase (ILK) in cancer progression". Cancer Metastasis Reviews 22 (4): 375–84. doi:10.1023/A:1023777013659. PMID 12884912.
• Srivastava D, Yu S (Sep 2006). "Stretching to meet needs: integrin-linked kinase and the cardiac pump". Genes & Development 20 (17): 2327–31. doi:10.1101/gad.1472506. PMID 16951248.
• Hannigan GE, Leung-Hagesteijn C, Fitz-Gibbon L, Coppolino MG, Radeva G, Filmus J, Bell JC, Dedhar S (Jan 1996). "Regulation of cell adhesion and anchorage-dependent growth by a new beta 1-integrin-linked protein kinase". Nature 379 (6560): 91–6. doi:10.1038/379091a0. PMID 8538749.
• Hannigan GE, Bayani J, Weksberg R, Beatty B, Pandita A, Dedhar S, Squire J (May 1997). "Mapping of the gene encoding the integrin-linked kinase, ILK, to human chromosome 11p15.5-p15.4". Genomics 42 (1): 177–9. doi:10.1006/geno.1997.4719. PMID 9177792.
• Li F, Liu J, Mayne R, Wu C (Oct 1997). "Identification and characterization of a mouse protein kinase that is highly homologous to human integrin-linked kinase". Biochimica Et Biophysica Acta 1358 (3): 215–20. doi:10.1016/S0167-4889(97)00089-X. PMID 9366252.
• Delcommenne M, Tan C, Gray V, Rue L, Woodgett J, Dedhar S (Sep 1998). "Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase". Proceedings of the National Academy of Sciences of the United States of America 95 (19): 11211–6. doi:10.1073/pnas.95.19.11211. PMC 21621. PMID 9736715.
• Chung DH, Lee JI, Kook MC, Kim JR, Kim SH, Choi EY, Park SH, Song HG (Aug 1998). "ILK (beta1-integrin-linked protein kinase): a novel immunohistochemical marker for Ewing's sarcoma and primitive neuroectodermal tumour". Virchows Archiv 433 (2): 113–7. doi:10.1007/s004280050225. PMID 9737788.
• Tu Y, Li F, Goicoechea S, Wu C (Mar 1999). "The LIM-only protein PINCH directly interacts with integrin-linked kinase and is recruited to integrin-rich sites in spreading cells". Molecular and Cellular Biology 19 (3): 2425–34. doi:10.1128/mcb.19.3.2425. PMC 84035. PMID 10022929.
• Feng J, Ito M, Ichikawa K, Isaka N, Nishikawa M, Hartshorne DJ, Nakano T (Dec 1999). "Inhibitory phosphorylation site for Rho-associated kinase on smooth muscle myosin phosphatase". The Journal of Biological Chemistry 274 (52): 37385–90. doi:10.1074/jbc.274.52.37385. PMID 10601309.
• Janji B, Melchior C, Vallar L, Kieffer N (Jun 2000). "Cloning of an isoform of integrin-linked kinase (ILK) that is upregulated in HT-144 melanoma cells following TGF-beta1 stimulation". Oncogene 19 (27): 3069–77. doi:10.1038/sj.onc.1203640. PMID 10871859.
• Velyvis A, Yang Y, Wu C, Qin J (Feb 2001). "Solution structure of the focal adhesion adaptor PINCH LIM1 domain and characterization of its interaction with the integrin-linked kinase ankyrin repeat domain". The Journal of Biological Chemistry 276 (7): 4932–9. doi:10.1074/jbc.M007632200. PMID 11078733.
• Matsumoto M, Ogawa W, Hino Y, Furukawa K, Ono Y, Takahashi M, Ohba M, Kuroki T, Kasuga M (Apr 2001). "Inhibition of insulin-induced activation of Akt by a kinase-deficient mutant of the epsilon isozyme of protein kinase C". The Journal of Biological Chemistry 276 (17): 14400–6. doi:10.1074/jbc.M011093200. PMID 11278835.
• Nikolopoulos SN, Turner CE (Jun 2001). "Integrin-linked kinase (ILK) binding to paxillin LD1 motif regulates ILK localization to focal adhesions". The Journal of Biological Chemistry 276 (26): 23499–505. doi:10.1074/jbc.M102163200. PMID 11304546.
• Persad S, Attwell S, Gray V, Mawji N, Deng JT, Leung D, Yan J, Sanghera J, Walsh MP, Dedhar S (Jul 2001). "Regulation of protein kinase B/Akt-serine 473 phosphorylation by integrin-linked kinase: critical roles for kinase activity and amino acids arginine 211 and serine 343". The Journal of Biological Chemistry 276 (29): 27462–9. doi:10.1074/jbc.M102940200. PMID 11313365.
• Tu Y, Huang Y, Zhang Y, Hua Y, Wu C (Apr 2001). "A new focal adhesion protein that interacts with integrin-linked kinase and regulates cell adhesion and spreading". The Journal of Cell Biology 153 (3): 585–98. doi:10.1083/jcb.153.3.585. PMC 2190577. PMID 11331308.
• Leung-Hagesteijn C, Mahendra A, Naruszewicz I, Hannigan GE (May 2001). "Modulation of integrin signal transduction by ILKAP, a protein phosphatase 2C associating with the integrin-linked kinase, ILK1". The EMBO Journal 20 (9): 2160–70. doi:10.1093/emboj/20.9.2160. PMC 125446. PMID 11331582.
• Yamaji S, Suzuki A, Sugiyama Y, Koide Y, Yoshida M, Kanamori H, Mohri H, Ohno S, Ishigatsubo Y (Jun 2001). "A novel integrin-linked kinase-binding protein, affixin, is involved in the early stage of cell-substrate interaction". The Journal of Cell Biology 153 (6): 1251–64. doi:10.1083/jcb.153.6.1251. PMC 2192033. PMID 11402068.
• Chen R, Kim O, Yang J, Sato K, Eisenmann KM, McCarthy J, Chen H, Qiu Y (Aug 2001). "Regulation of Akt/PKB activation by tyrosine phosphorylation". The Journal of Biological Chemistry 276 (34): 31858–62. doi:10.1074/jbc.C100271200. PMID 11445557.
• Fielding AB, Dobreva I, McDonald PC, Foster LJ, Dedhar S (Feb 2008). "Integrin-linked kinase localizes to the centrosome and regulates mitotic spindle organization". The Journal of Cell Biology 180 (4): 681–9. doi:10.1083/jcb.200710074. PMC 2265580. PMID 18283114.