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PMID: 21245141 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Up-regulation of AMP-activated protein kinase in cancer cell lines is mediated through c-Src activation.

The Journal of biological chemistry ·Vol. 286 ·No. 17 ·2011-04-29 ·Pages 15268-77

Mizrachy-Schwartz S, Cohen N, Klein S, Kravchenko-Balasha N, Levitzki A

Abstract

We report that the activation level of AMP-dependent protein kinase AMPK is elevated in cancer cell lines as a hallmark of their transformed state. In OVCAR3 and A431 cells, c-Src signals through protein kinase Cα, phospholipase Cγ, and LKB1 to AMPK. AMPK controls internal ribosome entry site (IRES) dependent translation in these cells. We suggest that AMPK activation via PKC might be a general mechanism to regulate IRES-dependent translation in cancer cells.

MeSH Terms
AMP-Activated Protein Kinases/genetics CSK Tyrosine-Protein Kinase Cell Line, Tumor Cell Transformation, Neoplastic Enzyme Activation/physiology Humans Protein Biosynthesis Protein-Tyrosine Kinases/metabolism Signal Transduction Up-Regulation/genetics src-Family Kinases
Chemicals
Protein-Tyrosine Kinases CSK Tyrosine-Protein Kinase src-Family Kinases CSK protein, human AMP-Activated Protein Kinases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Mizrachy-Schwartz Sarit
Unit of Cellular Signaling, Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Cohen Noam
Klein Shoshana
Kravchenko-Balasha Nataly
Levitzki Alexander
References (42)
42 references, click to expand
  1. Structure, function, and control of phosphoinositide-specific phospholipase C.
    Physiol Rev. 2000 Oct;80(4):1291-335 PMID: 11015615
  2. Divergent roles of c-Src in controlling platelet-derived growth factor-dependent signaling in fibroblasts.
    Mol Biol Cell. 2005 Nov;16(11):5418-32 PMID: 16135530
  3. Activation of protein kinase C zeta by peroxynitrite regulates LKB1-dependent AMP-activated protein kinase in cultured endothelial cells.
    J Biol Chem. 2006 Mar 10;281(10):6366-75 PMID: 16407220
  4. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.
    Anal Biochem. 1976 May 7;72:248-54 PMID: 942051
  5. GIT1 mediates VEGF-induced podosome formation in endothelial cells: critical role for PLCgamma.
    Arterioscler Thromb Vasc Biol. 2009 Feb;29(2):202-8 PMID: 19023093
  6. Activation of 5'-AMP-activated kinase is mediated through c-Src and phosphoinositide 3-kinase activity during hypoxia-reoxygenation of bovine aortic endothelial cells. Role of peroxynitrite.
    J Biol Chem. 2003 Sep 5;278(36):34003-10 PMID: 12824177
  7. The hunting of the Src.
    Nat Rev Mol Cell Biol. 2001 Jun;2(6):467-75 PMID: 11389470
  8. AMP-activated protein kinase activity is critical for hypoxia-inducible factor-1 transcriptional activity and its target gene expression under hypoxic conditions in DU145 cells.
    J Biol Chem. 2003 Oct 10;278(41):39653-61 PMID: 12900407
  9. Pyk2- and Src-dependent tyrosine phosphorylation of PDK1 regulates focal adhesions.
    Mol Cell Biol. 2003 Nov;23(22):8019-29 PMID: 14585963
  10. Combined inhibition of PLC{gamma}-1 and c-Src abrogates epidermal growth factor receptor-mediated head and neck squamous cell carcinoma invasion.
    Clin Cancer Res. 2008 Jul 1;14(13):4336-44 PMID: 18594017
  11. Activation of the AMP-activated protein kinase by the anti-diabetic drug metformin in vivo. Role of mitochondrial reactive nitrogen species.
    J Biol Chem. 2004 Oct 15;279(42):43940-51 PMID: 15265871
  12. Tumor suppressors and cell metabolism: a recipe for cancer growth.
    Genes Dev. 2009 Mar 1;23(5):537-48 PMID: 19270154
  13. Protein kinase C isotypes controlled by phosphoinositide 3-kinase through the protein kinase PDK1.
    Science. 1998 Sep 25;281(5385):2042-5 PMID: 9748166
  14. Linearization of the Bradford protein assay increases its sensitivity: theoretical and experimental studies.
    Anal Biochem. 1996 May 1;236(2):302-8 PMID: 8660509
  15. The road to Src.
    Oncogene. 2004 Oct 18;23(48):7910-7 PMID: 15489909
  16. Phosphorylation of LKB1 at serine 428 by protein kinase C-zeta is required for metformin-enhanced activation of the AMP-activated protein kinase in endothelial cells.
    Circulation. 2008 Feb 19;117(7):952-62 PMID: 18250273
  17. Activated SRC protein tyrosine kinase is overexpressed in late-stage human ovarian cancers.
    Gynecol Oncol. 2003 Jan;88(1):73-9 PMID: 12504632
  18. MO25alpha/beta interact with STRADalpha/beta enhancing their ability to bind, activate and localize LKB1 in the cytoplasm.
    EMBO J. 2003 Oct 1;22(19):5102-14 PMID: 14517248
  19. A role for phospholipase C-gamma-mediated signaling in tumor cell invasion.
    Clin Cancer Res. 1999 Aug;5(8):2251-60 PMID: 10473113
  20. Cancer's sweet tooth: the Janus effect of glucose metabolism in tumorigenesis.
    Lancet. 2006 Feb 18;367(9510):618-21 PMID: 16488806
  21. Epidermal-growth-factor-dependent activation of the src-family kinases.
    Eur J Biochem. 1994 Nov 1;225(3):1047-53 PMID: 7525285
  22. Hypoxia-inducible factor-1alpha mRNA contains an internal ribosome entry site that allows efficient translation during normoxia and hypoxia.
    Mol Biol Cell. 2002 May;13(5):1792-801 PMID: 12006670
  23. C75, a fatty acid synthase inhibitor, reduces food intake via hypothalamic AMP-activated protein kinase.
    J Biol Chem. 2004 May 7;279(19):19970-6 PMID: 15028725
  24. Regulation of 3-phosphoinositide-dependent protein kinase-1 (PDK1) by Src involves tyrosine phosphorylation of PDK1 and Src homology 2 domain binding.
    J Biol Chem. 2008 Jan 18;283(3):1480-1491 PMID: 18024423
  25. Akt activates the mammalian target of rapamycin by regulating cellular ATP level and AMPK activity.
    J Biol Chem. 2005 Sep 16;280(37):32081-9 PMID: 16027121
  26. Transformation of mouse cells by wild-type mouse c-Src.
    Oncogene. 1995 Jan 19;10(2):401-5 PMID: 7530829
  27. Discovery of a novel, potent, and Src family-selective tyrosine kinase inhibitor. Study of Lck- and FynT-dependent T cell activation.
    J Biol Chem. 1996 Jan 12;271(2):695-701 PMID: 8557675
  28. Upregulation and activation of PKC alpha by ErbB2 through Src promotes breast cancer cell invasion that can be blocked by combined treatment with PKC alpha and Src inhibitors.
    Oncogene. 2006 Jun 1;25(23):3286-95 PMID: 16407820
  29. Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade.
    J Biol. 2003;2(4):28 PMID: 14511394
  30. Interaction of estrogen receptor alpha with protein kinase C alpha and c-Src in osteoblasts during differentiation.
    Bone. 2004 Jan;34(1):100-11 PMID: 14751567
  31. Optimization of energy-consuming pathways towards rapid growth in HPV-transformed cells.
    PLoS One. 2007 Jul 11;2(7):e628 PMID: 17622357
  32. Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells.
    Cancer Res. 2007 Nov 15;67(22):10804-12 PMID: 18006825
  33. C-Myc 5' untranslated region contains an internal ribosome entry segment.
    Oncogene. 1998 Jan 22;16(3):423-8 PMID: 9467968
  34. Classical PKC isoforms in cancer.
    Pharmacol Res. 2007 Jun;55(6):477-86 PMID: 17548205
  35. Management of cellular energy by the AMP-activated protein kinase system.
    FEBS Lett. 2003 Jul 3;546(1):113-20 PMID: 12829246
  36. AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy.
    Nat Rev Mol Cell Biol. 2007 Oct;8(10):774-85 PMID: 17712357
  37. PDGF stimulation of inositol phospholipid hydrolysis requires PLC-gamma 1 phosphorylation on tyrosine residues 783 and 1254.
    Cell. 1991 May 3;65(3):435-41 PMID: 1708307
  38. Association of the insulin receptor with phospholipase C-gamma (PLCgamma) in 3T3-L1 adipocytes suggests a role for PLCgamma in metabolic signaling by insulin.
    J Biol Chem. 1998 May 29;273(22):13808-18 PMID: 9593725
  39. A renaissance for SRC.
    Nat Rev Cancer. 2004 Jun;4(6):470-80 PMID: 15170449
  40. Mnk2 and Mnk1 are essential for constitutive and inducible phosphorylation of eukaryotic initiation factor 4E but not for cell growth or development.
    Mol Cell Biol. 2004 Aug;24(15):6539-49 PMID: 15254222
  41. Activated pp60c-Src leads to elevated hypoxia-inducible factor (HIF)-1alpha expression under normoxia.
    J Biol Chem. 2002 Nov 8;277(45):42919-25 PMID: 12200433
  42. Regulation of conventional protein kinase C isozymes by phosphoinositide-dependent kinase 1 (PDK-1).
    Curr Biol. 1998 Dec 17-31;8(25):1366-75 PMID: 9889098
Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
1083-351X
DOI
10.1074/jbc.M110.211813
Published
2011-04-29
Epub
2011-00-18
Pages
15268-77
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC3083231
Subset
IM
External Links
PubMed source DOI: 10.1074/jbc.M110.211813 PMC Full Text View journal details
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