Integrin-linked kinase
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, signal transduction
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 encodes 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]
In 2008, ILK was found to localize to the centrosome and regulate mitotic spindle organization. [2]
Interactions
Integrin-linked kinase has been shown to interact with LIMS1,[3][4] AKT1,[5][6][7] ILKAP[8] and ACP6.[9]
References
- ^ "Entrez Gene: ILK integrin-linked kinase". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3611.
- ^ Fielding AB, Dobreva I, McDonald PC, Foster LJ, Dedhar S (February 2008). "Integrin-linked kinase localizes to the centrosome and regulates mitotic spindle organization". J. Cell Biol. 180 (4): 681–9. doi:10.1083/jcb.200710074. PMC 2265580. PMID 18283114. http://www.jcb.org/cgi/pmidlookup?view=long&pmid=18283114.
- ^ Tu, Y; Li F, Goicoechea S, Wu C (March 1999). "The LIM-Only Protein PINCH Directly Interacts with Integrin-Linked Kinase and Is Recruited to Integrin-Rich Sites in Spreading Cells". Mol. Cell. Biol. 19 (3): 2425–34. PMC 84035. PMID 10022929. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=84035.
- ^ Zhang, Yongjun; Chen Ka, Guo Lida, Wu Chuanyue (October 2002). "Characterization of PINCH-2, a new focal adhesion protein that regulates the PINCH-1-ILK interaction, cell spreading, and migration". J. Biol. Chem. 277 (41): 38328–38. doi:10.1074/jbc.M205576200. PMID 12167643.
- ^ Barry, Fiona A; Gibbins Jonathan M (April 2002). "Protein kinase B is regulated in platelets by the collagen receptor glycoprotein VI". J. Biol. Chem. 277 (15): 12874–8. doi:10.1074/jbc.M200482200. PMID 11825911.
- ^ Delcommenne, M; Tan C, Gray V, Rue L, Woodgett J, Dedhar S (September 1998). "Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase". Proc. Natl. Acad. Sci. U.S.A. 95 (19): 11211–6. doi:10.1073/pnas.95.19.11211. PMC 21621. PMID 9736715. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=21621.
- ^ Persad, S; Attwell S, Gray V, Mawji N, Deng J T, Leung D, Yan J, Sanghera J, Walsh M P, Dedhar S (July 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". J. Biol. Chem. 276 (29): 27462–9. doi:10.1074/jbc.M102940200. PMID 11313365.
- ^ Leung-Hagesteijn, C; Mahendra A, Naruszewicz I, Hannigan G E (May 2001). "Modulation of integrin signal transduction by ILKAP, a protein phosphatase 2C associating with the integrin-linked kinase, ILK1". EMBO J. 20 (9): 2160–70. doi:10.1093/emboj/20.9.2160. PMC 125446. PMID 11331582. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=125446.
- ^ Ewing, Rob M; Chu Peter, Elisma Fred, Li Hongyan, Taylor Paul, Climie Shane, McBroom-Cerajewski Linda, Robinson Mark D, O'Connor Liam, Li Michael, Taylor Rod, Dharsee Moyez, Ho Yuen, Heilbut Adrian, Moore Lynda, Zhang Shudong, Ornatsky Olga, Bukhman Yury V, Ethier Martin, Sheng Yinglun, Vasilescu Julian, Abu-Farha Mohamed, Lambert Jean-Philippe, Duewel Henry S, Stewart Ian I, Kuehl Bonnie, Hogue Kelly, Colwill Karen, Gladwish Katharine, Muskat Brenda, Kinach Robert, Adams Sally-Lin, Moran Michael F, Morin Gregg B, Topaloglou Thodoros, Figeys Daniel (2007). "Large-scale mapping of human protein–protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1847948.
Further reading
- Dedhar S (2000). "Cell-substrate interactions and signaling through ILK". Curr. Opin. Cell Biol. 12 (2): 250–6. doi:10.1016/S0955-0674(99)00083-6. PMID 10712922.
- Persad S, Dedhar S (2004). "The role of integrin-linked kinase (ILK) in cancer progression". Cancer Metastasis Rev. 22 (4): 375–84. doi:10.1023/A:1023777013659. PMID 12884912.
- Srivastava D, Yu S (2006). "Stretching to meet needs: integrin-linked kinase and the cardiac pump". Genes Dev. 20 (17): 2327–31. doi:10.1101/gad.1472506. PMID 16951248.
- Hannigan GE, Leung-Hagesteijn C, Fitz-Gibbon L, et al. (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, et al. (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 (1997). "Identification and characterization of a mouse protein kinase that is highly homologous to human integrin-linked kinase". Biochim. Biophys. Acta 1358 (3): 215–20. doi:10.1016/S0167-4889(97)00089-X. PMID 9366252.
- Delcommenne M, Tan C, Gray V, et al. (1998). "Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase". Proc. Natl. Acad. Sci. U.S.A. 95 (19): 11211–6. doi:10.1073/pnas.95.19.11211. PMC 21621. PMID 9736715. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=21621.
- Chung DH, Lee JI, Kook MC, et al. (1998). "ILK (beta1-integrin-linked protein kinase): a novel immunohistochemical marker for Ewing's sarcoma and primitive neuroectodermal tumour". Virchows Arch. 433 (2): 113–7. doi:10.1007/s004280050225. PMID 9737788.
- Tu Y, Li F, Goicoechea S, Wu C (1999). "The LIM-Only Protein PINCH Directly Interacts with Integrin-Linked Kinase and Is Recruited to Integrin-Rich Sites in Spreading Cells". Mol. Cell. Biol. 19 (3): 2425–34. PMC 84035. PMID 10022929. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=84035.
- Feng J, Ito M, Ichikawa K, et al. (2000). "Inhibitory phosphorylation site for Rho-associated kinase on smooth muscle myosin phosphatase". J. Biol. Chem. 274 (52): 37385–90. doi:10.1074/jbc.274.52.37385. PMID 10601309.
- Janji B, Melchior C, Vallar L, Kieffer N (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 (2001). "Solution structure of the focal adhesion adaptor PINCH LIM1 domain and characterization of its interaction with the integrin-linked kinase ankyrin repeat domain". J. Biol. Chem. 276 (7): 4932–9. doi:10.1074/jbc.M007632200. PMID 11078733.
- Matsumoto M, Ogawa W, Hino Y, et al. (2001). "Inhibition of insulin-induced activation of Akt by a kinase-deficient mutant of the epsilon isozyme of protein kinase C". J. Biol. Chem. 276 (17): 14400–6. doi:10.1074/jbc.M011093200. PMID 11278835.
- Nikolopoulos SN, Turner CE (2001). "Integrin-linked kinase (ILK) binding to paxillin LD1 motif regulates ILK localization to focal adhesions". J. Biol. Chem. 276 (26): 23499–505. doi:10.1074/jbc.M102163200. PMID 11304546.
- Persad S, Attwell S, Gray V, et al. (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". J. Biol. Chem. 276 (29): 27462–9. doi:10.1074/jbc.M102940200. PMID 11313365.
- Tu Y, Huang Y, Zhang Y, et al. (2001). "A New Focal Adhesion Protein That Interacts with Integrin-Linked Kinase and Regulates Cell Adhesion and Spreading". J. Cell Biol. 153 (3): 585–98. doi:10.1083/jcb.153.3.585. PMC 2190577. PMID 11331308. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2190577.
- Leung-Hagesteijn C, Mahendra A, Naruszewicz I, Hannigan GE (2001). "Modulation of integrin signal transduction by ILKAP, a protein phosphatase 2C associating with the integrin-linked kinase, ILK1". EMBO J. 20 (9): 2160–70. doi:10.1093/emboj/20.9.2160. PMC 125446. PMID 11331582. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=125446.
- Yamaji S, Suzuki A, Sugiyama Y, et al. (2001). "A Novel Integrin-Linked Kinase–Binding Protein, Affixin, Is Involved in the Early Stage of Cell–Substrate Interaction". J. Cell Biol. 153 (6): 1251–64. doi:10.1083/jcb.153.6.1251. PMC 2192033. PMID 11402068. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2192033.
- Chen R, Kim O, Yang J, et al. (2001). "Regulation of Akt/PKB activation by tyrosine phosphorylation". J. Biol. Chem. 276 (34): 31858–62. doi:10.1074/jbc.C100271200. PMID 11445557.
- Fielding A, Dobreva I, McDonald PC, et al. (2008). "Integrin-linked kinase localizes to the centrosome and regulates mitotic spindle organization". J. Cell Biol. 180 (4): 681–9. doi:10.1083/jcb.200710074. PMC 2265580. PMID 18283114. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2265580.