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Biochem J. Nov 1, 1995; 311(Pt 3): 735–738.
PMCID: PMC1136064

The activation of distinct mitogen-activated protein kinase cascades is required for the stimulation of 2-deoxyglucose uptake by interleukin-1 and insulin-like growth factor-1 in KB cells.


The uptake of 2-deoxyglucose into KB cells was stimulated about 2-fold by interleukin-1 (IL1), anisomycin or insulin-like growth factor-1 (IGF1). Stimulation by IL1 and anisomycin was prevented by SB 203580, a specific inhibitor of the mitogen-activated protein (MAP) kinase homologue termed 're-activating kinase' [RK; also known as p38, p40 and CSBP (cytokine synthesis anti-inflammatory-drug-binding protein)], but was unaffected by PD 98059, a specific inhibitor of the activation of the classical MAP kinase pathway. In contrast, the stimulation of 2-deoxyglucose uptake by IGF1 was blocked by PD 98059 and unaffected by SB 203580. Consistent with these observations, IL1 and anisomycin were potent activators of MAP kinase-activated protein (MAPKAP) kinase-2, a physiological substrate of RK, whereas IGF1 was only a very weak activator of MAPKAP kinase-2. Conversely, IGF1 was a stronger activator of p42 MAP kinase than IL1 or anisomycin. These results imply that the activation of distinct MAP kinase pathways is required for the stimulation of glucose transport by IL1/anisomycin and IGF1 in KB cells, and suggest that the combined use of SB 203580 and PD 98059 is a powerful new approach to explore the roles of different MAP kinase cascades in cell regulation.

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  • Kyriakis JM, Banerjee P, Nikolakaki E, Dai T, Rubie EA, Ahmad MF, Avruch J, Woodgett JR. The stress-activated protein kinase subfamily of c-Jun kinases. Nature. 1994 May 12;369(6476):156–160. [PubMed]
  • Galcheva-Gargova Z, Dérijard B, Wu IH, Davis RJ. An osmosensing signal transduction pathway in mammalian cells. Science. 1994 Aug 5;265(5173):806–808. [PubMed]
  • Kracht M, Truong O, Totty NF, Shiroo M, Saklatvala J. Interleukin 1 alpha activates two forms of p54 alpha mitogen-activated protein kinase in rabbit liver. J Exp Med. 1994 Dec 1;180(6):2017–2025. [PMC free article] [PubMed]
  • Han J, Lee JD, Bibbs L, Ulevitch RJ. A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science. 1994 Aug 5;265(5173):808–811. [PubMed]
  • Rouse J, Cohen P, Trigon S, Morange M, Alonso-Llamazares A, Zamanillo D, Hunt T, Nebreda AR. A novel kinase cascade triggered by stress and heat shock that stimulates MAPKAP kinase-2 and phosphorylation of the small heat shock proteins. Cell. 1994 Sep 23;78(6):1027–1037. [PubMed]
  • Freshney NW, Rawlinson L, Guesdon F, Jones E, Cowley S, Hsuan J, Saklatvala J. Interleukin-1 activates a novel protein kinase cascade that results in the phosphorylation of Hsp27. Cell. 1994 Sep 23;78(6):1039–1049. [PubMed]
  • Cuenda A, Rouse J, Doza YN, Meier R, Cohen P, Gallagher TF, Young PR, Lee JC. SB 203580 is a specific inhibitor of a MAP kinase homologue which is stimulated by cellular stresses and interleukin-1. FEBS Lett. 1995 May 8;364(2):229–233. [PubMed]
  • Raingeaud J, Gupta S, Rogers JS, Dickens M, Han J, Ulevitch RJ, Davis RJ. Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine. J Biol Chem. 1995 Mar 31;270(13):7420–7426. [PubMed]
  • Dérijard B, Hibi M, Wu IH, Barrett T, Su B, Deng T, Karin M, Davis RJ. JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell. 1994 Mar 25;76(6):1025–1037. [PubMed]
  • Stokoe D, Engel K, Campbell DG, Cohen P, Gaestel M. Identification of MAPKAP kinase 2 as a major enzyme responsible for the phosphorylation of the small mammalian heat shock proteins. FEBS Lett. 1992 Nov 30;313(3):307–313. [PubMed]
  • Lavoie JN, Lambert H, Hickey E, Weber LA, Landry J. Modulation of cellular thermoresistance and actin filament stability accompanies phosphorylation-induced changes in the oligomeric structure of heat shock protein 27. Mol Cell Biol. 1995 Jan;15(1):505–516. [PMC free article] [PubMed]
  • Weinstein SL, Sanghera JS, Lemke K, DeFranco AL, Pelech SL. Bacterial lipopolysaccharide induces tyrosine phosphorylation and activation of mitogen-activated protein kinases in macrophages. J Biol Chem. 1992 Jul 25;267(21):14955–14962. [PubMed]
  • Saklatvala J, Rawlinson LM, Marshall CJ, Kracht M. Interleukin 1 and tumour necrosis factor activate the mitogen-activated protein (MAP) kinase kinase in cultured cells. FEBS Lett. 1993 Nov 15;334(2):189–192. [PubMed]
  • Dubois MF, Bensaude O. MAP kinase activation during heat shock in quiescent and exponentially growing mammalian cells. FEBS Lett. 1993 Jun 14;324(2):191–195. [PubMed]
  • Sánchez I, Hughes RT, Mayer BJ, Yee K, Woodgett JR, Avruch J, Kyriakis JM, Zon LI. Role of SAPK/ERK kinase-1 in the stress-activated pathway regulating transcription factor c-Jun. Nature. 1994 Dec 22;372(6508):794–798. [PubMed]
  • Dérijard B, Raingeaud J, Barrett T, Wu IH, Han J, Ulevitch RJ, Davis RJ. Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms. Science. 1995 Feb 3;267(5198):682–685. [PubMed]
  • Yan M, Dai T, Deak JC, Kyriakis JM, Zon LI, Woodgett JR, Templeton DJ. Activation of stress-activated protein kinase by MEKK1 phosphorylation of its activator SEK1. Nature. 1994 Dec 22;372(6508):798–800. [PubMed]
  • Matsuda S, Kawasaki H, Moriguchi T, Gotoh Y, Nishida E. Activation of protein kinase cascades by osmotic shock. J Biol Chem. 1995 May 26;270(21):12781–12786. [PubMed]
  • Minden A, Lin A, McMahon M, Lange-Carter C, Dérijard B, Davis RJ, Johnson GL, Karin M. Differential activation of ERK and JNK mitogen-activated protein kinases by Raf-1 and MEKK. Science. 1994 Dec 9;266(5191):1719–1723. [PubMed]
  • Lee JC, Laydon JT, McDonnell PC, Gallagher TF, Kumar S, Green D, McNulty D, Blumenthal MJ, Heys JR, Landvatter SW, et al. A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature. 1994 Dec 22;372(6508):739–746. [PubMed]
  • Stokoe D, Caudwell B, Cohen PT, Cohen P. The substrate specificity and structure of mitogen-activated protein (MAP) kinase-activated protein kinase-2. Biochem J. 1993 Dec 15;296(Pt 3):843–849. [PMC free article] [PubMed]
  • Alessi DR, Cohen P, Ashworth A, Cowley S, Leevers SJ, Marshall CJ. Assay and expression of mitogen-activated protein kinase, MAP kinase kinase, and Raf. Methods Enzymol. 1995;255:279–290. [PubMed]
  • Gibbs EM, Lienhard GE, Gould GW. Insulin-induced translocation of glucose transporters to the plasma membrane precedes full stimulation of hexose transport. Biochemistry. 1988 Sep 6;27(18):6681–6685. [PubMed]
  • Bloch R. Inhibition of glucose transport in the human erythrocyte by cytochalasin B. Biochemistry. 1973 Nov 6;12(23):4799–4801. [PubMed]
  • Guesdon F, Freshney N, Waller RJ, Rawlinson L, Saklatvala J. Interleukin 1 and tumor necrosis factor stimulate two novel protein kinases that phosphorylate the heat shock protein hsp27 and beta-casein. J Biol Chem. 1993 Feb 25;268(6):4236–4243. [PubMed]
  • Bird TA, Kyriakis JM, Tyshler L, Gayle M, Milne A, Virca GD. Interleukin-1 activates p54 mitogen-activated protein (MAP) kinase/stress-activated protein kinase by a pathway that is independent of p21ras, Raf-1, and MAP kinase kinase. J Biol Chem. 1994 Dec 16;269(50):31836–31844. [PubMed]
  • Mahadevan LC, Edwards DR. Signalling and superinduction. Nature. 1991 Feb 28;349(6312):747–748. [PubMed]
  • Merrall NW, Plevin RJ, Stokoe D, Cohen P, Nebreda AR, Gould GW. Mitogen-activated protein kinase (MAP kinase), MAP kinase kinase and c-Mos stimulate glucose transport in Xenopus oocytes. Biochem J. 1993 Oct 15;295(Pt 2):351–355. [PMC free article] [PubMed]
  • Lazar DF, Wiese RJ, Brady MJ, Mastick CC, Waters SB, Yamauchi K, Pessin JE, Cuatrecasas P, Saltiel AR. Mitogen-activated protein kinase kinase inhibition does not block the stimulation of glucose utilization by insulin. J Biol Chem. 1995 Sep 1;270(35):20801–20807. [PubMed]

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