Mouse Erk-1 gene product is a serine/threonine protein kinase that has the potential to phosphorylate tyrosine (original) (raw)

Abstract

Bacterial expression of mouse gene Erk-1 yielded an active kinase with the same substrate specificity shown for ERK1 protein purified from rat cells. Although rat gene ERK1 is believed to encode a serine/threonine kinase based on sequence data and known ERK1 substrate phosphorylation sites, bacterially-produced mouse Erk-1 (bt-Erk-1) autophosphorylated on tyrosine in addition to serine and threonine residues. The bt-Erk-1 protein also had the capacity to reactivate the ribosomal protein S6 kinase (S6KII). Furthermore, treatment of bt-Erk-1 with either serine/threonine-specific phosphatase 2A or tyrosine-specific phosphatase 1B significantly decreased its kinase activity. These findings predict that autophosphorylation may play an important role in Erk-1/ERK1 regulation.

8845

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ahn N. G., Seger R., Bratlien R. L., Diltz C. D., Tonks N. K., Krebs E. G. Multiple components in an epidermal growth factor-stimulated protein kinase cascade. In vitro activation of a myelin basic protein/microtubule-associated protein 2 kinase. J Biol Chem. 1991 Mar 5;266(7):4220–4227. [PubMed] [Google Scholar]
  2. Ahn N. G., Weiel J. E., Chan C. P., Krebs E. G. Identification of multiple epidermal growth factor-stimulated protein serine/threonine kinases from Swiss 3T3 cells. J Biol Chem. 1990 Jul 15;265(20):11487–11494. [PubMed] [Google Scholar]
  3. Anderson N. G., Maller J. L., Tonks N. K., Sturgill T. W. Requirement for integration of signals from two distinct phosphorylation pathways for activation of MAP kinase. Nature. 1990 Feb 15;343(6259):651–653. doi: 10.1038/343651a0. [DOI] [PubMed] [Google Scholar]
  4. Ben-David Y., Letwin K., Tannock L., Bernstein A., Pawson T. A mammalian protein kinase with potential for serine/threonine and tyrosine phosphorylation is related to cell cycle regulators. EMBO J. 1991 Feb;10(2):317–325. doi: 10.1002/j.1460-2075.1991.tb07952.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Boulton T. G., Gregory J. S., Cobb M. H. Purification and properties of extracellular signal-regulated kinase 1, an insulin-stimulated microtubule-associated protein 2 kinase. Biochemistry. 1991 Jan 8;30(1):278–286. doi: 10.1021/bi00215a038. [DOI] [PubMed] [Google Scholar]
  6. Boulton T. G., Nye S. H., Robbins D. J., Ip N. Y., Radziejewska E., Morgenbesser S. D., DePinho R. A., Panayotatos N., Cobb M. H., Yancopoulos G. D. ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF. Cell. 1991 May 17;65(4):663–675. doi: 10.1016/0092-8674(91)90098-j. [DOI] [PubMed] [Google Scholar]
  7. Boulton T. G., Yancopoulos G. D., Gregory J. S., Slaughter C., Moomaw C., Hsu J., Cobb M. H. An insulin-stimulated protein kinase similar to yeast kinases involved in cell cycle control. Science. 1990 Jul 6;249(4964):64–67. doi: 10.1126/science.2164259. [DOI] [PubMed] [Google Scholar]
  8. Chernoff J., Li H. C., Cheng Y. S., Chen L. B. Characterization of a phosphotyrosyl protein phosphatase activity associated with a phosphoseryl protein phosphatase of Mr = 95,000 from bovine heart. J Biol Chem. 1983 Jun 25;258(12):7852–7857. [PubMed] [Google Scholar]
  9. Courchesne W. E., Kunisawa R., Thorner J. A putative protein kinase overcomes pheromone-induced arrest of cell cycling in S. cerevisiae. Cell. 1989 Sep 22;58(6):1107–1119. doi: 10.1016/0092-8674(89)90509-6. [DOI] [PubMed] [Google Scholar]
  10. Dailey D., Schieven G. L., Lim M. Y., Marquardt H., Gilmore T., Thorner J., Martin G. S. Novel yeast protein kinase (YPK1 gene product) is a 40-kilodalton phosphotyrosyl protein associated with protein-tyrosine kinase activity. Mol Cell Biol. 1990 Dec;10(12):6244–6256. doi: 10.1128/mcb.10.12.6244. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Elion E. A., Grisafi P. L., Fink G. R. FUS3 encodes a cdc2+/CDC28-related kinase required for the transition from mitosis into conjugation. Cell. 1990 Feb 23;60(4):649–664. doi: 10.1016/0092-8674(90)90668-5. [DOI] [PubMed] [Google Scholar]
  12. Ely C. M., Oddie K. M., Litz J. S., Rossomando A. J., Kanner S. B., Sturgill T. W., Parsons S. J. A 42-kD tyrosine kinase substrate linked to chromaffin cell secretion exhibits an associated MAP kinase activity and is highly related to a 42-kD mitogen-stimulated protein in fibroblasts. J Cell Biol. 1990 Mar;110(3):731–742. doi: 10.1083/jcb.110.3.731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Erickson A. K., Payne D. M., Martino P. A., Rossomando A. J., Shabanowitz J., Weber M. J., Hunt D. F., Sturgill T. W. Identification by mass spectrometry of threonine 97 in bovine myelin basic protein as a specific phosphorylation site for mitogen-activated protein kinase. J Biol Chem. 1990 Nov 15;265(32):19728–19735. [PubMed] [Google Scholar]
  14. Featherstone C., Russell P. Fission yeast p107wee1 mitotic inhibitor is a tyrosine/serine kinase. Nature. 1991 Feb 28;349(6312):808–811. doi: 10.1038/349808a0. [DOI] [PubMed] [Google Scholar]
  15. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  16. Gotoh Y., Nishida E., Matsuda S., Shiina N., Kosako H., Shiokawa K., Akiyama T., Ohta K., Sakai H. In vitro effects on microtubule dynamics of purified Xenopus M phase-activated MAP kinase. Nature. 1991 Jan 17;349(6306):251–254. doi: 10.1038/349251a0. [DOI] [PubMed] [Google Scholar]
  17. Gotoh Y., Nishida E., Yamashita T., Hoshi M., Kawakami M., Sakai H. Microtubule-associated-protein (MAP) kinase activated by nerve growth factor and epidermal growth factor in PC12 cells. Identity with the mitogen-activated MAP kinase of fibroblastic cells. Eur J Biochem. 1990 Nov 13;193(3):661–669. doi: 10.1111/j.1432-1033.1990.tb19384.x. [DOI] [PubMed] [Google Scholar]
  18. Hanks S. K., Quinn A. M., Hunter T. The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science. 1988 Jul 1;241(4861):42–52. doi: 10.1126/science.3291115. [DOI] [PubMed] [Google Scholar]
  19. Haystead T. A., Weiel J. E., Litchfield D. W., Tsukitani Y., Fischer E. H., Krebs E. G. Okadaic acid mimics the action of insulin in stimulating protein kinase activity in isolated adipocytes. The role of protein phosphatase 2a in attenuation of the signal. J Biol Chem. 1990 Sep 25;265(27):16571–16580. [PubMed] [Google Scholar]
  20. Hoshi M., Nishida E., Sakai H. Characterization of a mitogen-activated, Ca2+-sensitive microtubule-associated protein-2 kinase. Eur J Biochem. 1989 Sep 15;184(2):477–486. doi: 10.1111/j.1432-1033.1989.tb15040.x. [DOI] [PubMed] [Google Scholar]
  21. Howell B. W., Afar D. E., Lew J., Douville E. M., Icely P. L., Gray D. A., Bell J. C. STY, a tyrosine-phosphorylating enzyme with sequence homology to serine/threonine kinases. Mol Cell Biol. 1991 Jan;11(1):568–572. doi: 10.1128/mcb.11.1.568. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kamps M. P., Sefton B. M. Acid and base hydrolysis of phosphoproteins bound to immobilon facilitates analysis of phosphoamino acids in gel-fractionated proteins. Anal Biochem. 1989 Jan;176(1):22–27. doi: 10.1016/0003-2697(89)90266-2. [DOI] [PubMed] [Google Scholar]
  23. Kim H., Binder L. I., Rosenbaum J. L. The periodic association of MAP2 with brain microtubules in vitro. J Cell Biol. 1979 Feb;80(2):266–276. doi: 10.1083/jcb.80.2.266. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  25. Landreth G. E., Smith D. S., McCabe C., Gittinger C. Characterization of a nerve growth factor-stimulated protein kinase in PC12 cells which phosphorylates microtubule-associated protein 2 and pp250. J Neurochem. 1990 Aug;55(2):514–523. doi: 10.1111/j.1471-4159.1990.tb04165.x. [DOI] [PubMed] [Google Scholar]
  26. Lundgren K., Walworth N., Booher R., Dembski M., Kirschner M., Beach D. mik1 and wee1 cooperate in the inhibitory tyrosine phosphorylation of cdc2. Cell. 1991 Mar 22;64(6):1111–1122. doi: 10.1016/0092-8674(91)90266-2. [DOI] [PubMed] [Google Scholar]
  27. Miyasaka T., Chao M. V., Sherline P., Saltiel A. R. Nerve growth factor stimulates a protein kinase in PC-12 cells that phosphorylates microtubule-associated protein-2. J Biol Chem. 1990 Mar 15;265(8):4730–4735. [PubMed] [Google Scholar]
  28. Payne D. M., Rossomando A. J., Martino P., Erickson A. K., Her J. H., Shabanowitz J., Hunt D. F., Weber M. J., Sturgill T. W. Identification of the regulatory phosphorylation sites in pp42/mitogen-activated protein kinase (MAP kinase). EMBO J. 1991 Apr;10(4):885–892. doi: 10.1002/j.1460-2075.1991.tb08021.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ray L. B., Sturgill T. W. Characterization of insulin-stimulated microtubule-associated protein kinase. Rapid isolation and stabilization of a novel serine/threonine kinase from 3T3-L1 cells. J Biol Chem. 1988 Sep 5;263(25):12721–12727. [PubMed] [Google Scholar]
  30. Ray L. B., Sturgill T. W. Insulin-stimulated microtubule-associated protein kinase is phosphorylated on tyrosine and threonine in vivo. Proc Natl Acad Sci U S A. 1988 Jun;85(11):3753–3757. doi: 10.1073/pnas.85.11.3753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Ray L. B., Sturgill T. W. Rapid stimulation by insulin of a serine/threonine kinase in 3T3-L1 adipocytes that phosphorylates microtubule-associated protein 2 in vitro. Proc Natl Acad Sci U S A. 1987 Mar;84(6):1502–1506. doi: 10.1073/pnas.84.6.1502. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sanghera J. S., Paddon H. B., Pelech S. L. Role of protein phosphorylation in the maturation-induced activation of a myelin basic protein kinase from sea star oocytes. J Biol Chem. 1991 Apr 15;266(11):6700–6707. [PubMed] [Google Scholar]
  34. Seger R., Ahn N. G., Boulton T. G., Yancopoulos G. D., Panayotatos N., Radziejewska E., Ericsson L., Bratlien R. L., Cobb M. H., Krebs E. G. Microtubule-associated protein 2 kinases, ERK1 and ERK2, undergo autophosphorylation on both tyrosine and threonine residues: implications for their mechanism of activation. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6142–6146. doi: 10.1073/pnas.88.14.6142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Smith D. B., Johnson K. S. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. Gene. 1988 Jul 15;67(1):31–40. doi: 10.1016/0378-1119(88)90005-4. [DOI] [PubMed] [Google Scholar]
  36. Stern D. F., Zheng P., Beidler D. R., Zerillo C. Spk1, a new kinase from Saccharomyces cerevisiae, phosphorylates proteins on serine, threonine, and tyrosine. Mol Cell Biol. 1991 Feb;11(2):987–1001. doi: 10.1128/mcb.11.2.987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Sturgill T. W., Ray L. B., Erikson E., Maller J. L. Insulin-stimulated MAP-2 kinase phosphorylates and activates ribosomal protein S6 kinase II. Nature. 1988 Aug 25;334(6184):715–718. doi: 10.1038/334715a0. [DOI] [PubMed] [Google Scholar]
  38. Toda T., Shimanuki M., Yanagida M. Fission yeast genes that confer resistance to staurosporine encode an AP-1-like transcription factor and a protein kinase related to the mammalian ERK1/MAP2 and budding yeast FUS3 and KSS1 kinases. Genes Dev. 1991 Jan;5(1):60–73. doi: 10.1101/gad.5.1.60. [DOI] [PubMed] [Google Scholar]
  39. Tung H. Y., Resink T. J., Hemmings B. A., Shenolikar S., Cohen P. The catalytic subunits of protein phosphatase-1 and protein phosphatase 2A are distinct gene products. Eur J Biochem. 1984 Feb 1;138(3):635–641. doi: 10.1111/j.1432-1033.1984.tb07962.x. [DOI] [PubMed] [Google Scholar]