Phosphorylation at Threonine-235 by a Ras-dependent Mitogen-activated Protein Kinase Cascade is Essential for Transcription Factor NF-IL6

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1993 Mar 15

PMID 8384717

Citations 163

Authors

T Nakajima

S Kinoshita

T Sasagawa

K Sasaki

M Naruto

T Kishimoto

S Akira

Affiliations

Soon will be listed here.

Abstract

NF-IL6, a member of the basic leucine zipper (bZIP) family transcription factors, is involved in expression of inducible genes involved in immune and inflammatory responses. We observed that coexpression of oncogenic p21ras stimulated the transactivating activity of NF-IL6 and induced phosphorylation of Thr-235 located just N-terminal to the DNA binding domain of NF-IL6. Recently, mitogen-activated protein (MAP) kinases have been shown to be implicated in the cellular response to activated ras. Purified MAP kinases specifically phosphorylated Thr-235 of NF-IL6 in vitro. Mutation of Thr-235 abolished the ras-dependent activation of NF-IL6. From these results, we conclude that NF-IL6 is regulated through phosphorylation by MAP kinases in response to activated ras.

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References

Taga T, Hibi M, Hirata Y, Yamasaki K, Yasukawa K, Matsuda T . Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130. Cell. 1989; 58(3):573-81. DOI: 10.1016/0092-8674(89)90438-8. View

Taga T, Narazaki M, Yasukawa K, Saito T, Miki D, Hamaguchi M . Functional inhibition of hematopoietic and neurotrophic cytokines by blocking the interleukin 6 signal transducer gp130. Proc Natl Acad Sci U S A. 1992; 89(22):10998-1001. PMC: 50470. DOI: 10.1073/pnas.89.22.10998. View

Akira S, Isshiki H, Sugita T, TANABE O, Kinoshita S, Nishio Y . A nuclear factor for IL-6 expression (NF-IL6) is a member of a C/EBP family. EMBO J. 1990; 9(6):1897-906. PMC: 551896. DOI: 10.1002/j.1460-2075.1990.tb08316.x. View

Poli V, Mancini F, Cortese R . IL-6DBP, a nuclear protein involved in interleukin-6 signal transduction, defines a new family of leucine zipper proteins related to C/EBP. Cell. 1990; 63(3):643-53. DOI: 10.1016/0092-8674(90)90459-r. View

Chang C, Chen T, Lei H, Chen D, Lee S . Molecular cloning of a transcription factor, AGP/EBP, that belongs to members of the C/EBP family. Mol Cell Biol. 1990; 10(12):6642-53. PMC: 362942. DOI: 10.1128/mcb.10.12.6642-6653.1990. View

Descombes P, Chojkier M, LICHTSTEINER S, Falvey E, Schibler U . LAP, a novel member of the C/EBP gene family, encodes a liver-enriched transcriptional activator protein. Genes Dev. 1990; 4(9):1541-51. DOI: 10.1101/gad.4.9.1541. View

Hibi M, Murakami M, Saito M, Hirano T, Taga T, Kishimoto T . Molecular cloning and expression of an IL-6 signal transducer, gp130. Cell. 1990; 63(6):1149-57. DOI: 10.1016/0092-8674(90)90411-7. View

Bourne H, Sanders D, McCormick F . The GTPase superfamily: conserved structure and molecular mechanism. Nature. 1991; 349(6305):117-27. DOI: 10.1038/349117a0. View

Cantley L, Auger K, Carpenter C, Duckworth B, Graziani A, Kapeller R . Oncogenes and signal transduction. Cell. 1991; 64(2):281-302. DOI: 10.1016/0092-8674(91)90639-g. View

10.

Boyle W, Smeal T, Defize L, Angel P, Woodgett J, Karin M . Activation of protein kinase C decreases phosphorylation of c-Jun at sites that negatively regulate its DNA-binding activity. Cell. 1991; 64(3):573-84. DOI: 10.1016/0092-8674(91)90241-p. View

11.

Isshiki H, Akira S, Sugita T, Nishio Y, Hashimoto S, Pawlowski T . Reciprocal expression of NF-IL6 and C/EBP in hepatocytes: possible involvement of NF-IL6 in acute phase protein gene expression. New Biol. 1991; 3(1):63-70. View

12.

Sturgill T, Wu J . Recent progress in characterization of protein kinase cascades for phosphorylation of ribosomal protein S6. Biochim Biophys Acta. 1991; 1092(3):350-7. DOI: 10.1016/s0167-4889(97)90012-4. View

13.

Alvarez E, Northwood I, Gonzalez F, Latour D, Seth A, Abate C . Pro-Leu-Ser/Thr-Pro is a consensus primary sequence for substrate protein phosphorylation. Characterization of the phosphorylation of c-myc and c-jun proteins by an epidermal growth factor receptor threonine 669 protein kinase. J Biol Chem. 1991; 266(23):15277-85. View

14.

Cao Z, Umek R, McKnight S . Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells. Genes Dev. 1991; 5(9):1538-52. DOI: 10.1101/gad.5.9.1538. View

15.

Williams S, Cantwell C, Johnson P . A family of C/EBP-related proteins capable of forming covalently linked leucine zipper dimers in vitro. Genes Dev. 1991; 5(9):1553-67. DOI: 10.1101/gad.5.9.1553. View

16.

Metz R, Ziff E . cAMP stimulates the C/EBP-related transcription factor rNFIL-6 to trans-locate to the nucleus and induce c-fos transcription. Genes Dev. 1991; 5(10):1754-66. DOI: 10.1101/gad.5.10.1754. View

17.

Pulverer B, Kyriakis J, Avruch J, Nikolakaki E, Woodgett J . Phosphorylation of c-jun mediated by MAP kinases. Nature. 1991; 353(6345):670-4. DOI: 10.1038/353670a0. View

18.

Rossomando A, Sanghera J, Marsden L, Weber M, Pelech S, Sturgill T . Biochemical characterization of a family of serine/threonine protein kinases regulated by tyrosine and serine/threonine phosphorylations. J Biol Chem. 1991; 266(30):20270-5. View

19.

Gonzalez F, Raden D, Davis R . Identification of substrate recognition determinants for human ERK1 and ERK2 protein kinases. J Biol Chem. 1991; 266(33):22159-63. View

20.

Sturgill T, Ray L, Anderson N, Erickson A . Purification of mitogen-activated protein kinase from epidermal growth factor-treated 3T3-L1 fibroblasts. Methods Enzymol. 1991; 200:342-51. DOI: 10.1016/0076-6879(91)00151-l. View