Phosphorylation of Ser-42 and Ser-59 in the N-terminal region of the tyrosine kinase p56lck (original) (raw)

Abstract

Ser-42 and Ser-59 in the N-terminal region have been identified as the major phorbol ester-induced phosphorylation sites of p56lck. Phosphorylation of Ser-59 results in a gel shift from 56 kDa to 61 kDa. Simultaneous phosphorylation of Ser-42 and Ser-59 results in a further gel shift to 63 kDa. In vitro kinase assays show that Ser-59 can be uniquely phosphorylated by mitogen-activated protein kinase and that Ser-42 can be phosphorylated by either protein kinase A or protein kinase C.

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Selected References

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  1. Bramson H. N., Casnellie J. E., Nachod H., Regan L. M., Sommers C. Synthetic fragments of the CD4 receptor cytoplasmic domain and large polycations alter the activities of the pp56lck tyrosine protein kinase. J Biol Chem. 1991 Aug 25;266(24):16219–16225. [PubMed] [Google Scholar]
  2. Casnellie J. E., Lamberts R. J. Tumor promoters cause changes in the state of phosphorylation and apparent molecular weight of a tyrosine protein kinase in T lymphocytes. J Biol Chem. 1986 Apr 15;261(11):4921–4925. [PubMed] [Google Scholar]
  3. Casnellie J. E. Sites of in vivo phosphorylation of the T cell tyrosine protein kinase in LSTRA cells and their alteration by tumor-promoting phorbol esters. J Biol Chem. 1987 Jul 15;262(20):9859–9864. [PubMed] [Google Scholar]
  4. Chackalaparampil I., Shalloway D. Altered phosphorylation and activation of pp60c-src during fibroblast mitosis. Cell. 1988 Mar 25;52(6):801–810. doi: 10.1016/0092-8674(88)90422-9. [DOI] [PubMed] [Google Scholar]
  5. Einspahr K. J., Abraham R. T., Dick C. J., Leibson P. J. Protein tyrosine phosphorylation and p56lck modification in IL-2 or phorbol ester-activated human natural killer cells. J Immunol. 1990 Sep 1;145(5):1490–1497. [PubMed] [Google Scholar]
  6. Ettehadieh E., Sanghera J. S., Pelech S. L., Hess-Bienz D., Watts J., Shastri N., Aebersold R. Tyrosyl phosphorylation and activation of MAP kinases by p56lck. Science. 1992 Feb 14;255(5046):853–855. doi: 10.1126/science.1311128. [DOI] [PubMed] [Google Scholar]
  7. Gould K. L., Woodgett J. R., Cooper J. A., Buss J. E., Shalloway D., Hunter T. Protein kinase C phosphorylates pp60src at a novel site. Cell. 1985 Oct;42(3):849–857. doi: 10.1016/0092-8674(85)90281-8. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Horak I. D., Gress R. E., Lucas P. J., Horak E. M., Waldmann T. A., Bolen J. B. T-lymphocyte interleukin 2-dependent tyrosine protein kinase signal transduction involves the activation of p56lck. Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1996–2000. doi: 10.1073/pnas.88.5.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. House C., Wettenhall R. E., Kemp B. E. The influence of basic residues on the substrate specificity of protein kinase C. J Biol Chem. 1987 Jan 15;262(2):772–777. [PubMed] [Google Scholar]
  11. Hurley T. R., Luo K., Sefton B. M. Activators of protein kinase C induce dissociation of CD4, but not CD8, from p56lck. Science. 1989 Jul 28;245(4916):407–409. doi: 10.1126/science.2787934. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Koch C. A., Anderson D., Moran M. F., Ellis C., Pawson T. SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins. Science. 1991 May 3;252(5006):668–674. doi: 10.1126/science.1708916. [DOI] [PubMed] [Google Scholar]
  14. Kunkel T. A. Rapid and efficient site-specific mutagenesis without phenotypic selection. Proc Natl Acad Sci U S A. 1985 Jan;82(2):488–492. doi: 10.1073/pnas.82.2.488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Luo K. X., Sefton B. M. Analysis of the sites in p56lck whose phosphorylation is induced by tetradecanoyl phorbol acetate. Oncogene. 1990 Jun;5(6):803–808. [PubMed] [Google Scholar]
  16. Luo K., Hurley T. R., Sefton B. M. Transfer of proteins to membranes facilitates both cyanogen bromide cleavage and two-dimensional proteolytic mapping. Oncogene. 1990 Jun;5(6):921–923. [PubMed] [Google Scholar]
  17. Morgan D. O., Kaplan J. M., Bishop J. M., Varmus H. E. Mitosis-specific phosphorylation of p60c-src by p34cdc2-associated protein kinase. Cell. 1989 Jun 2;57(5):775–786. doi: 10.1016/0092-8674(89)90792-7. [DOI] [PubMed] [Google Scholar]
  18. Patschinsky T., Hunter T., Sefton B. M. Phosphorylation of the transforming protein of Rous sarcoma virus: direct demonstration of phosphorylation of serine 17 and identification of an additional site of tyrosine phosphorylation in p60v-src of Prague Rous sarcoma virus. J Virol. 1986 Jul;59(1):73–81. doi: 10.1128/jvi.59.1.73-81.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Payne G., Shoelson S. E., Gish G. D., Pawson T., Walsh C. T. Kinetics of p56lck and p60src Src homology 2 domain binding to tyrosine-phosphorylated peptides determined by a competition assay or surface plasmon resonance. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):4902–4906. doi: 10.1073/pnas.90.11.4902. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Purchio A. F., Shoyab M., Gentry L. E. Site-specific increased phosphorylation of pp60v-src after treatment of RSV-transformed cells with a tumor promoter. Science. 1985 Sep 27;229(4720):1393–1395. doi: 10.1126/science.2994221. [DOI] [PubMed] [Google Scholar]
  21. Ramer S. E., Winkler D. G., Carrera A., Roberts T. M., Walsh C. T. Purification and initial characterization of the lymphoid-cell protein-tyrosine kinase p56lck from a baculovirus expression system. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6254–6258. doi: 10.1073/pnas.88.14.6254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Shenoy S., Choi J. K., Bagrodia S., Copeland T. D., Maller J. L., Shalloway D. Purified maturation promoting factor phosphorylates pp60c-src at the sites phosphorylated during fibroblast mitosis. Cell. 1989 Jun 2;57(5):763–774. doi: 10.1016/0092-8674(89)90791-5. [DOI] [PubMed] [Google Scholar]
  23. Shin J., Doyle C., Yang Z., Kappes D., Strominger J. L. Structural features of the cytoplasmic region of CD4 required for internalization. EMBO J. 1990 Feb;9(2):425–434. doi: 10.1002/j.1460-2075.1990.tb08127.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Shin J., Dunbrack R. L., Jr, Lee S., Strominger J. L. Phosphorylation-dependent down-modulation of CD4 requires a specific structure within the cytoplasmic domain of CD4. J Biol Chem. 1991 Jun 5;266(16):10658–10665. [PubMed] [Google Scholar]
  25. Sleckman B. P., Shin J., Igras V. E., Collins T. L., Strominger J. L., Burakoff S. J. Disruption of the CD4-p56lck complex is required for rapid internalization of CD4. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7566–7570. doi: 10.1073/pnas.89.16.7566. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Turner J. M., Brodsky M. H., Irving B. A., Levin S. D., Perlmutter R. M., Littman D. R. Interaction of the unique N-terminal region of tyrosine kinase p56lck with cytoplasmic domains of CD4 and CD8 is mediated by cysteine motifs. Cell. 1990 Mar 9;60(5):755–765. doi: 10.1016/0092-8674(90)90090-2. [DOI] [PubMed] [Google Scholar]
  27. Veillette A., Horak I. D., Horak E. M., Bookman M. A., Bolen J. B. Alterations of the lymphocyte-specific protein tyrosine kinase (p56lck) during T-cell activation. Mol Cell Biol. 1988 Oct;8(10):4353–4361. doi: 10.1128/mcb.8.10.4353. [DOI] [PMC free article] [PubMed] [Google Scholar]