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Insulin activates a novel adipocyte mitogen-activated protein kinase kinase kinase that shows rapid phasic kinetics and is distinct from c-Raf.

Publication ,  Journal Article
Haystead, CM; Gregory, P; Shirazi, A; Fadden, P; Mosse, C; Dent, P; Haystead, TA
Published in: J Biol Chem
April 29, 1994

Treatment of adipocytes with insulin or phorbol 12-myristate 13-acetate (PMA) results in transient activation of mitogen-activated protein kinase kinase (MEK) (Tmax = 90 s) and mitogen-activated protein kinase (MAPK) (Tmax = 300 s). We have identified a novel insulin-stimulated MEK kinase (I-MEKK) in the 100,000 x g infranatant that shows rapid phasic kinetics that temporally precede that of MEK. Maximal activation of I-MEKK occurs within 20 +/- 5 s (S.D., n = 3) followed by complete inactivation by 30 +/- 10 s (S.D., n = 3). I-MEKK was characterized by anion-exchange and gel filtration chromatography and separated into two distinct activities of approximately 56 kDa that phosphorylated and activated MEK. I-MEKKs did not co-elute on anion exchange with c-Raf or 73-kDa MEK kinase (MEKK), suggesting they are distinct enzymes. Protein phosphatase 2A inactivated both I-MEKKs in vitro and in the intact cell okadaic acid blocked inactivation in the presence of insulin. These results suggest activation of I-MEKK involves phosphorylation on serine or threonine residues. I-MEKK was not activated by PMA, suggesting that in adipocytes the enzyme represents a divergence point between signal transduction pathways mediated by insulin and those activating protein kinase C.

Duke Scholars

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

April 29, 1994

Volume

269

Issue

17

Start / End Page

12804 / 12808

Location

United States

Related Subject Headings

  • Tetradecanoylphorbol Acetate
  • Rats, Wistar
  • Rats
  • Proto-Oncogene Proteins c-raf
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • Protein Phosphatase 2
  • Phosphoprotein Phosphatases
  • Mitogen-Activated Protein Kinase Kinases
 

Citation

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MLA
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Haystead, C. M., Gregory, P., Shirazi, A., Fadden, P., Mosse, C., Dent, P., & Haystead, T. A. (1994). Insulin activates a novel adipocyte mitogen-activated protein kinase kinase kinase that shows rapid phasic kinetics and is distinct from c-Raf. J Biol Chem, 269(17), 12804–12808.
Haystead, C. M., P. Gregory, A. Shirazi, P. Fadden, C. Mosse, P. Dent, and T. A. Haystead. “Insulin activates a novel adipocyte mitogen-activated protein kinase kinase kinase that shows rapid phasic kinetics and is distinct from c-Raf.J Biol Chem 269, no. 17 (April 29, 1994): 12804–8.
Haystead CM, Gregory P, Shirazi A, Fadden P, Mosse C, Dent P, et al. Insulin activates a novel adipocyte mitogen-activated protein kinase kinase kinase that shows rapid phasic kinetics and is distinct from c-Raf. J Biol Chem. 1994 Apr 29;269(17):12804–8.
Haystead CM, Gregory P, Shirazi A, Fadden P, Mosse C, Dent P, Haystead TA. Insulin activates a novel adipocyte mitogen-activated protein kinase kinase kinase that shows rapid phasic kinetics and is distinct from c-Raf. J Biol Chem. 1994 Apr 29;269(17):12804–12808.

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

April 29, 1994

Volume

269

Issue

17

Start / End Page

12804 / 12808

Location

United States

Related Subject Headings

  • Tetradecanoylphorbol Acetate
  • Rats, Wistar
  • Rats
  • Proto-Oncogene Proteins c-raf
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • Protein Phosphatase 2
  • Phosphoprotein Phosphatases
  • Mitogen-Activated Protein Kinase Kinases