The Secret Life of Kinases: Functions Beyond Catalysis

Overview

Journal Cell Commun Signal

Publisher Biomed Central

Specialties Biochemistry
Cell Biology

Date 2011 Nov 1

PMID 22035226

Citations 100

Authors

Jens Rauch

Natalia Volinsky

David Romano

Walter Kolch

Affiliations

Soon will be listed here.

Abstract

Protein phosphorylation participates in the regulation of all fundamental biological processes, and protein kinases have been intensively studied. However, while the focus was on catalytic activities, accumulating evidence suggests that non-catalytic properties of protein kinases are essential, and in some cases even sufficient for their functions. These non-catalytic functions include the scaffolding of protein complexes, the competition for protein interactions, allosteric effects on other enzymes, subcellular targeting, and DNA binding. This rich repertoire often is used to coordinate phosphorylation events and enhance the specificity of substrate phosphorylation, but also can adopt functions that do not rely on kinase activity. Here, we discuss such kinase independent functions of protein and lipid kinases focussing on kinases that play a role in the regulation of cell proliferation, differentiation, apoptosis, and motility.

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References

Harvey A, Crompton M . Use of RNA interference to validate Brk as a novel therapeutic target in breast cancer: Brk promotes breast carcinoma cell proliferation. Oncogene. 2003; 22(32):5006-10. DOI: 10.1038/sj.onc.1206577. View

Gingras A, Raught B, Sonenberg N . Regulation of translation initiation by FRAP/mTOR. Genes Dev. 2001; 15(7):807-26. DOI: 10.1101/gad.887201. View

Shapiro P, Whalen A, Tolwinski N, Wilsbacher J, Froelich-Ammon S, Garcia M . Extracellular signal-regulated kinase activates topoisomerase IIalpha through a mechanism independent of phosphorylation. Mol Cell Biol. 1999; 19(5):3551-60. PMC: 84147. DOI: 10.1128/MCB.19.5.3551. View

Lange A, Wickstrom S, Jakobson M, Zent R, Sainio K, Fassler R . Integrin-linked kinase is an adaptor with essential functions during mouse development. Nature. 2009; 461(7266):1002-6. DOI: 10.1038/nature08468. View

Arteaga C . Epidermal growth factor receptor dependence in human tumors: more than just expression?. Oncologist. 2002; 7 Suppl 4:31-9. DOI: 10.1634/theoncologist.7-suppl_4-31. View

Liu P, Cheng H, Roberts T, Zhao J . Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009; 8(8):627-44. PMC: 3142564. DOI: 10.1038/nrd2926. View

Koch C, Anderson D, Moran M, Ellis C, Pawson T . SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins. Science. 1991; 252(5006):668-74. DOI: 10.1126/science.1708916. View

Coso O, Chiariello M, Yu J, Teramoto H, Crespo P, Xu N . The small GTP-binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signaling pathway. Cell. 1995; 81(7):1137-46. DOI: 10.1016/s0092-8674(05)80018-2. View

Manning G, Whyte D, Martinez R, Hunter T, Sudarsanam S . The protein kinase complement of the human genome. Science. 2002; 298(5600):1912-34. DOI: 10.1126/science.1075762. View

10.

Monetti M, Nagaraj N, Sharma K, Mann M . Large-scale phosphosite quantification in tissues by a spike-in SILAC method. Nat Methods. 2011; 8(8):655-8. DOI: 10.1038/nmeth.1647. View

11.

Liu Y, Chen N, Cui X, Zheng X, Deng L, Price S . The protein kinase Pak4 disrupts mammary acinar architecture and promotes mammary tumorigenesis. Oncogene. 2010; 29(44):5883-94. PMC: 2974003. DOI: 10.1038/onc.2010.329. View

12.

Meloche S, Pouyssegur J . The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1- to S-phase transition. Oncogene. 2007; 26(22):3227-39. DOI: 10.1038/sj.onc.1210414. View

13.

A Crackower M, Oudit G, Kozieradzki I, Sarao R, Sun H, Sasaki T . Regulation of myocardial contractility and cell size by distinct PI3K-PTEN signaling pathways. Cell. 2002; 110(6):737-49. DOI: 10.1016/s0092-8674(02)00969-8. View

14.

Klein T, Jenny A, Djiane A, Mlodzik M . CKIepsilon/discs overgrown promotes both Wnt-Fz/beta-catenin and Fz/PCP signaling in Drosophila. Curr Biol. 2006; 16(13):1337-43. DOI: 10.1016/j.cub.2006.06.030. View

15.

Grashoff C, Aszodi A, Sakai T, Hunziker E, Fassler R . Integrin-linked kinase regulates chondrocyte shape and proliferation. EMBO Rep. 2003; 4(4):432-8. PMC: 1319157. DOI: 10.1038/sj.embor.embor801. View

16.

Matsumoto R, Wang D, Blonska M, Li H, Kobayashi M, Pappu B . Phosphorylation of CARMA1 plays a critical role in T Cell receptor-mediated NF-kappaB activation. Immunity. 2005; 23(6):575-85. DOI: 10.1016/j.immuni.2005.10.007. View

17.

Bromann P, Korkaya H, Courtneidge S . The interplay between Src family kinases and receptor tyrosine kinases. Oncogene. 2004; 23(48):7957-68. DOI: 10.1038/sj.onc.1208079. View

18.

Rauch J, ONeill E, Mack B, Matthias C, Munz M, Kolch W . Heterogeneous nuclear ribonucleoprotein H blocks MST2-mediated apoptosis in cancer cells by regulating A-Raf transcription. Cancer Res. 2010; 70(4):1679-88. PMC: 2880479. DOI: 10.1158/0008-5472.CAN-09-2740. View

19.

Miettinen P, Berger J, Meneses J, Phung Y, Pedersen R, Werb Z . Epithelial immaturity and multiorgan failure in mice lacking epidermal growth factor receptor. Nature. 1995; 376(6538):337-41. DOI: 10.1038/376337a0. View

20.

Brunton V, Avizienyte E, Fincham V, Serrels B, Metcalf 3rd C, Sawyer T . Identification of Src-specific phosphorylation site on focal adhesion kinase: dissection of the role of Src SH2 and catalytic functions and their consequences for tumor cell behavior. Cancer Res. 2005; 65(4):1335-42. DOI: 10.1158/0008-5472.CAN-04-1949. View