Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

3-Phosphoinositide-Dependent Kinase 1 (PDK1)

  • Aikaterini Emmanouilidi
  • Marco Falasca
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101748

Synonyms

Historical Background

The 3-phosphoinositide-dependent kinase-1 (PDK1) is a well-studied member of the AGC kinase subfamily which is implicated in many physiological functions and when dysregulated can play a role in cancer, among other pathological conditions. The AGC kinases can act on tyrosine (Tyr), serine (Ser), or threonine (Thr) residues of their substrates and comprise of 60 members, for most of which there are a number of splice variants isoforms. For the majority of the AGC kinases, phosphorylation of the T-loop in the catalytic domain and the hydrophobic motif in the noncatalytic region leads to activation of the kinase. Apart from these two highly conserved motifs, the turn motif can also be phosphorylated in several members of the ACG kinases family. In regard to interaction with their substrates, the specificity of the kinases is determined by the residues in the peptide binding...

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References

  1. Arteaga CL, Johnson MD, Todderud G, Coffey RJ, Carpenter G, Page DL. Elevated content of the tyrosine kinase substrate phospholipase C-gamma 1 in primary human breast carcinomas. Proc Natl Acad Sci USA. 1991;88(23):10435.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Calleja V, Laguerre M, de Las Heras-Martinez G, Parker PJ, Requejo-Isidro J, Larijani B. Acute regulation of PDK1 by a complex interplay of molecular switches. Biochem Soc Trans. 2014;42(5):1435.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Cohen P, Alessi DR, Cross DAE. PDK1, one of the missing links in insulin signal transduction? FEBS Lett. 1997;410:3–10. 1 The previous Datta Lectures were given by: F. Melchers 1997(1st, 1986), N. Sharon (2nd, FEBS Lett. 217 (1987) 145–157)C.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Eser S, Reiff N, Messer M, Seidler B, Gottschalk K, Dobler M, et al. Selective requirement of PI3K/PDK1 signaling for kras oncogene-driven pancreatic cell plasticity and cancer. Cancer Cell. 2013;23(3):406–20.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Ferro R, Falasca M. Emerging role of the KRAS-PDK1 axis in pancreatic cancer. World J Gastroenterol. 2014;20(31):10752.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Gagliardi PA, di Blasio L, Puliafito A, Seano G, Sessa R, Chianale F, et al. PDK1-mediated activation of MRCKα regulates directional cell migration and lamellipodia retraction. J Cell Biol. 2014;206(3):415–34.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Gagliardi PA, Di Blasio L, Primo L. PDK1: A signaling hub for cell migration and tumor invasion. BBA – Rev Cancer. 2015;1856(2):178–88.Google Scholar
  8. Kikani CK, Verona EV, Ryu J, Shen Y, Ye Q, Zheng L, et al. Proliferative and antiapoptotic signaling stimulated by nuclear-localized PDK1 results in oncogenesis. Sci Signal. 2012;5(249):ra80.PubMedPubMedCentralCrossRefGoogle Scholar
  9. King CC, Newton AC. The adaptor protein Grb14 regulates the localization of 3-phosphoinositide-dependent kinase-1. J Biol Chem. 2004;279(36):37518–27.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Kung M-L, Tsai H-E, Hu T-H, Kuo H-M, Liu L-F, Chen S-C, et al. Hepatoma-derived growth factor stimulates podosome rosettes formation in NIH/3T3 cells through the activation of phosphatidylinositol 3-kinase/Akt pathway. Biochem Biophys Res Commun. 2012;425(2):169–76.CrossRefPubMedGoogle Scholar
  11. Maurer M, Su T, Saal LH, Koujak S, Hopkins BD, Barkley CR, et al. 3-phosphoinositide–dependent kinase 1 potentiates upstream lesions on the phosphatidylinositol 3-kinase pathway in breast carcinoma. Cancer Res. 2009;69(15):6299–306.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Murphy DA, Courtneidge SA. The ‘ins’ and ‘outs’ of podosomes and invadopodia: characteristics, formation and function. Nat Rev Mol Cell Biol. 2011;12(7):413–26.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Pearce LR, Komander D, Alessi DR. The nuts and bolts of AGC protein kinases. Nat Rev Mol Cell Biol. 2010;11(1):9.CrossRefPubMedGoogle Scholar
  14. Pinner S, Sahai E. PDK1 regulates cancer cell motility by antagonising inhibition of ROCK1 by RhoE. Nat Cell Biol. 2008;10(2):127–37.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Raimondi C, Chikh A, Wheeler AP, Maffucci T, Falasca M. A novel regulatory mechanism links PLCγ1 to PDK1. J Cell Sci. 2012;125(Pt 13):3153.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Sahai E, Marshall CJ. Differing modes of tumour cell invasion have distinct requirements for Rho/ROCK signalling and extracellular proteolysis. Nat Cell Biol. 2003;5(8):711–9.CrossRefPubMedGoogle Scholar
  17. Sala G, Dituri F, Raimondi C, Previdi S, Maffucci T, Mazzoletti M, et al. Phospholipase Cγ1 is required for metastasis development and progression. Cancer Res. 2008;68(24):10187–96.CrossRefPubMedGoogle Scholar
  18. Yamaguchi H, Yoshida S, Muroi E, Yoshida N, Kawamura M, Kouchi Z, et al. Phosphoinositide 3-kinase signaling pathway mediated by p110α regulates invadopodia formation. J Cell Biol. 2011;193(7):1275–88.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.School of Biomedical Sciences, Metabolic Signalling GroupCurtin University, Faculty of Health SciencesPerthAustralia