Insulin stimulates the activity of mitogen-activated protein kinase (MAPK) via its upstream activator, MAPK kinase (MEK), a dual specificity kinase that phosphorylates MAPK on threonine and tyrosine. The potential role of MAPK activation in insulin action was investigated with the specific MEK inhibitor PD98059. Insulin stimulation of MAPK activity in 3T3-L1 adipocytes (2.7-fold) and L6 myotubes (1.4-fold) was completely abolished by pretreatment of cells with the MEK inhibitor, as was the phosphorylation of MAPK and pp90, and the transcriptional activation of c-fos. Insulin receptor autophosphorylation on tyrosine residues and activation of phosphatidylinositol 3`-kinase were unaffected. Pretreatment of cells with PD98059 had no effect on basal and insulin-stimulated glucose uptake, lipogenesis, and glycogen synthesis. Glycogen synthase activity in extracts from 3T3-L1 adipocytes and L6 myotubes was increased 3-fold and 1.7-fold, respectively, by insulin. Pretreatment with 10 µM PD98059 was without effect. Similarly, the 2-fold activation of protein phosphatase 1 by insulin was insensitive to PD98059. These results indicate that stimulation of the MAPK pathway by insulin is not required for many of the metabolic activities of the hormone in cultured fat and muscle cells.

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				M. J. Brady, A. C. Nairn, and A. R. Saltiel The Regulation of Glycogen Synthase by Protein Phosphatase 1 in 3T3-L1 Adipocytes. EVIDENCE FOR A POTENTIAL ROLE FOR DARPP-32 IN INSULIN ACTION J. Biol. Chem., November 21, 1997; 272(47): 29698 - 29703. [Abstract] [Full Text] [PDF]

				K.-C. Leung, M. J. Waters, I. Markus, W. R. Baumbach, and K. K. Y. Ho Insulin and insulin-like growth factor-I acutely inhibit surface translocation of growth hormone receptors in osteoblasts: A novel mechanism of growth hormone receptor regulation PNAS, October 14, 1997; 94(21): 11381 - 11386. [Abstract] [Full Text] [PDF]

				N. Hemati, S. E. Ross, R. L. Erickson, G. E. Groblewski, and O. A. MacDougald Signaling Pathways through Which Insulin Regulates CCAAT/Enhancer Binding Protein alpha  (C/EBPalpha ) Phosphorylation and Gene Expression in 3T3-L1 Adipocytes. CORRELATION WITH GLUT4 GENE EXPRESSION J. Biol. Chem., October 10, 1997; 272(41): 25913 - 25919. [Abstract] [Full Text] [PDF]

				T. Bellido, V. Z. C. Borba, P. Roberson, and S. C. Manolagas Activation of the Janus Kinase/STAT (Signal Transducer and Activator of Transcription) Signal Transduction Pathway by Interleukin-6-Type Cytokines Promotes Osteoblast Differentiation Endocrinology, September 1, 1997; 138(9): 3666 - 3676. [Abstract] [Full Text] [PDF]

				M. J. Brady, J. A. Printen, C. C. Mastick, and A. R. Saltiel Role of Protein Targeting to Glycogen (PTG) in the Regulation of Protein Phosphatase-1 Activity J. Biol. Chem., August 8, 1997; 272(32): 20198 - 20204. [Abstract] [Full Text] [PDF]

				M. Ohmichi, K. Koike, A. Kimura, K. Masuhara, H. Ikegami, Y. Ikebuchi, T. Kanzaki, K. Touhara, M. Sakaue, Y. Kobayashi, et al. Role of Mitogen-Activated Protein Kinase Pathway in Prostaglandin F2{alpha}-Induced Rat Puerperal Uterine Contraction Endocrinology, August 1, 1997; 138(8): 3103 - 3111. [Abstract] [Full Text] [PDF]

				L. Ragolia and N. Begum The Effect of Modulating the Glycogen-Associated Regulatory Subunit of Protein Phosphatase-1 on Insulin Action in Rat Skeletal Muscle Cells Endocrinology, June 1, 1997; 138(6): 2398 - 2404. [Abstract] [Full Text] [PDF]

				A. W. Kao, S. B. Waters, S. Okada, and J. E. Pessin Insulin Stimulates the Phosphorylation of the 66- and 52-Kilodalton Shc Isoforms by Distinct Pathways Endocrinology, June 1, 1997; 138(6): 2474 - 2480. [Abstract] [Full Text] [PDF]

				Y. Takahashi, Y. Okimura, I. Mizuno, K. Iida, T. Takahashi, H. Kaji, H. Abe, and K. Chihara Leptin Induces Mitogen-activated Protein Kinase- dependent Proliferation of C3H10T1/2 Cells J. Biol. Chem., May 16, 1997; 272(20): 12897 - 12900. [Abstract] [Full Text] [PDF]

				C. Ravanat, M. Morales, D. O. Azorsa, S. Moog, S. Schuhler, P. Grunert, D. Loew, A. Van Dorsselaer, J.-P. Cazenave, and F. Lanza Gene Cloning of Rat and Mouse Platelet Glycoprotein V: Identification of Megakaryocyte-Specific Promoters and Demonstration of Functional Thrombin Cleavage Blood, May 1, 1997; 89(9): 3253 - 3262. [Abstract] [Full Text] [PDF]

				H. S. Camp and S. R. Tafuri Regulation of Peroxisome Proliferator-activated Receptor gamma Activity by Mitogen-activated Protein Kinase J. Biol. Chem., April 18, 1997; 272(16): 10811 - 10816. [Abstract] [Full Text] [PDF]

				C. Knall, G. S. Worthen, and G. L. Johnson Interleukin 8-stimulated phosphatidylinositol-3-kinase activity regulates the migration of human neutrophils independent of extracellular signal-regulated kinase and p38 mitogen-activated protein kinases PNAS, April 1, 1997; 94(7): 3052 - 3057. [Abstract] [Full Text] [PDF]

				R. W. Brownsey, A. N. Boone, and M. F. Allard Actions of insulin on the mammalian heart: metabolism, pathology and biochemical mechanisms Cardiovasc Res, April 1, 1997; 34(1): 3 - 24. [Full Text] [PDF]

				S. A. Coolican, D. S. Samuel, D. Z. Ewton, F. J. McWade, and J. R. Florini The Mitogenic and Myogenic Actions of Insulin-like Growth Factors Utilize Distinct Signaling Pathways J. Biol. Chem., March 7, 1997; 272(10): 6653 - 6662. [Abstract] [Full Text] [PDF]

				V. I. Shifrin, R. J. Davis, and B. G. Neel Phosphorylation of Protein-tyrosine Phosphatase PTP-1B on Identical Sites Suggests Activation of a Common Signaling Pathway during Mitosis and Stress Response in Mammalian Cells J. Biol. Chem., January 31, 1997; 272(5): 2957 - 2962. [Abstract] [Full Text] [PDF]

				L. Gnudi, E. U. Frevert, K. L. Houseknecht, P. Erhardt, and B. B. Kahn Adenovirus-Mediated Gene Transfer of Dominant Negative Rasasn17 in 3T3L1 Adipocytes Does Not Alter Insulin-Stimulated PI3-Kinase Activity or Glucose Transport Mol. Endocrinol., January 1, 1997; 11(1): 67 - 76. [Abstract] [Full Text]

				K. Graf, X.-P. Xi, D. Yang, E. Fleck, W. A. Hsueh, and R. E. Law Mitogen-Activated Protein Kinase Activation Is Involved in Platelet-Derived Growth Factor-Directed Migration by Vascular Smooth Muscle Cells Hypertension, January 1, 1997; 29(1): 334 - 339. [Abstract] [Full Text] [PDF]

				A. D. Kohn, S. A. Summers, M. J. Birnbaum, and R. A. Roth Expression of a Constitutively Active Akt Ser/Thr Kinase in 3T3-L1 Adipocytes Stimulates Glucose Uptake and Glucose Transporter 4Translocation J. Biol. Chem., December 6, 1996; 271(49): 31372 - 31378. [Abstract] [Full Text] [PDF]

				C. M. Moxham, A. Tabrizchi, R. J. Davis, and CraigC. Malbon jun N-terminal Kinase Mediates Activation of Skeletal Muscle Glycogen Synthase by Insulin in Vivo J. Biol. Chem., November 29, 1996; 271(48): 30765 - 30773. [Abstract] [Full Text] [PDF]

				S. Harada, R. M. Smith, J. A. Smith, M. F. White, and L. Jarett Insulin-induced egr-1 and c-fos Expression in 32D Cells Requires Insulin Receptor, Shc, and Mitogen-activated Protein Kinase, but Not Insulin Receptor Substrate-1 and Phosphatidylinositol 3-Kinase Activation J. Biol. Chem., November 22, 1996; 271(47): 30222 - 30226. [Abstract] [Full Text] [PDF]

				J.-F. Tanti, T. Gremeaux, S. Grillo, V. Calleja, A. Klippel, L. T. Williams, E. Van Obberghen, and Y. Le Marchand-Brustel Overexpression of a Constitutively Active Form of Phosphatidylinositol 3-Kinase Is Sufficient to Promote Glut 4Translocation in Adipocytes J. Biol. Chem., October 11, 1996; 271(41): 25227 - 25232. [Abstract] [Full Text] [PDF]

				V. Lefebvre, M.-C. Mechin, M. P. Louckx, M. H. Rider, and L. Hue Signaling Pathway Involved in the Activation of Heart 6-Phosphofructo-2-kinase by Insulin J. Biol. Chem., September 13, 1996; 271(37): 22289 - 22292. [Abstract] [Full Text] [PDF]

				G. J. Bhat, S. T. Abraham, and K. M. Baker Angiotensin II Interferes with Interleukin 6-induced Stat3 Signaling by a Pathway Involving Mitogen-activated Protein Kinase Kinase 1 J. Biol. Chem., September 13, 1996; 271(37): 22447 - 22452. [Abstract] [Full Text] [PDF]

				J. Si, Z. Luo, and L. Mei Induction of Acetylcholine Receptor Gene Expression by ARIA Requires Activation of Mitogen-activated Protein Kinase J. Biol. Chem., August 16, 1996; 271(33): 19752 - 19759. [Abstract] [Full Text] [PDF]

				O. Aharonovitz and Y. Granot Stimulation of Mitogen-activated Protein Kinase and Na+/H+ Exchanger in Human Platelets. DIFFERENTIAL EFFECT OF PHORBOL ESTER AND VASOPRESSIN J. Biol. Chem., July 12, 1996; 271(28): 16494 - 16499. [Abstract] [Full Text] [PDF]

				J. K. Klarlund, A. D. Cherniack, M. McMahon, and M. P. Czech Role of the Raf/Mitogen-activated Protein Kinase Pathway in p21ras Desensitization J. Biol. Chem., July 12, 1996; 271(28): 16674 - 16677. [Abstract] [Full Text] [PDF]