Crossref journal-article
American Association for the Advancement of Science (AAAS)
Science (221)
Abstract

Entry into mitosis in Schizosaccharomyces pombe is negatively regulated by the wee1 + gene, which encodes a protein kinase with serine-, theonine-, and tyrosine-phosphorylating activities. The wee1 + kinase negatively regulates mitosis by phosphorylating p34 cdc2 on tyrosine 15, thereby inactivating the p34 cdc2 -cyclin B complex. The human homolog of the wee1 + gene ( WEE1Hu ) was overproduced in bacteria and assayed in an in vitro system. Unlike its fission yeast homolog, the product of the WEE1Hu gene encoded a tyrosine-specific protein kinase. The human WEE1 kinase phosphorylated the p34 cdc2 -cyclin B complex on tyrosine 15 but not on threonine 14 in vitro and inactivated the p34 cdc2 -cyclin B kinase. This inhibition was reversed by the human Cdc25C protein, which catalyzed the dephosphorylation of p34 cdc2 . These results indicate that the product of the WEE1Hu gene directly regulates the p34 cdc2 -cyclin B complex in human cells and that a kinase other than that encoded by WEE1Hu phosphorylates p34 cdc2 on threonine 14.

Bibliography

Parker, L. L., & Piwnica-Worms, H. (1992). Inactivation of the p34 cdc2 -Cyclin B Complex by the Human WEE1 Tyrosine Kinase. Science, 257(5078), 1955–1957.

Authors 2
  1. Laura L. Parker (first)
  2. Helen Piwnica-Worms (additional)
References 27 Referenced 548
  1. BOOHER, R, SITE-SPECIFIC MUTAGENESIS OF CDC2+, A CELL-CYCLE CONTROL GENE OF THE FISSION YEAST SCHIZOSACCHAROMYCES-POMBE, MOLECULAR AND CELLULAR BIOLOGY 6: 3523 (1986). / MOLECULAR AND CELLULAR BIOLOGY (1986)
  2. DUCOMMUN, B, CDC2 PHOSPHORYLATION IS REQUIRED FOR ITS INTERACTION WITH CYCLIN, EMBO JOURNAL 10: 3311 (1991). (10.1002/j.1460-2075.1991.tb04895.x) / EMBO JOURNAL (1991)
  3. FEATHERSTONE, C, FISSION YEAST P107WEE1 MITOTIC INHIBITOR IS A TYROSINE SERINE KINASE, NATURE 349: 808 (1991). (10.1038/349808a0) / NATURE (1991)
  4. GALAKTIONOV, K, SPECIFIC ACTIVATION OF CDC25 TYROSINE PHOSPHATASES BY B-TYPE CYCLINS - EVIDENCE FOR MULTIPLE ROLES OF MITOTIC CYCLINS, CELL 67: 1181 (1991). (10.1016/0092-8674(91)90294-9) / CELL (1991)
  5. GAUTIER, J, CDC25 IS A SPECIFIC TYROSINE PHOSPHATASE THAT DIRECTLY ACTIVATES P34CDC2, CELL 67: 197 (1991). (10.1016/0092-8674(91)90583-K) / CELL (1991)
  6. GOULD, K.L., PHOSPHORYLATION AT THR167 IS REQUIRED FOR SCHIZOSACCHAROMYCES-POMBE P34CDC2 FUNCTION, EMBO JOURNAL 10: 3297 (1991). (10.1002/j.1460-2075.1991.tb04894.x) / EMBO JOURNAL (1991)
  7. IGARASHI, M, WEE1+-LIKE GENE IN HUMAN-CELLS, NATURE 353: 80 (1991). (10.1038/353080a0) / NATURE (1991)
  8. KOFF, A, HUMAN CYCLIN-E, A NEW CYCLIN THAT INTERACTS WITH 2 MEMBERS OF THE CDC2 GENE FAMILY, CELL 66: 1217 (1991). (10.1016/0092-8674(91)90044-Y) / CELL (1991)
  9. 10.1002/j.1460-2075.1991.tb07951.x
  10. KREK, W, EMBO J 10: 3321 (1991). (10.1002/j.1460-2075.1991.tb04896.x) / EMBO J (1991)
  11. KREK, W, MUTATIONS OF P34CDC2 PHOSPHORYLATION SITES INDUCE PREMATURE MITOTIC EVENTS IN HELA-CELLS - EVIDENCE FOR A DOUBLE BLOCK TO P34CDC2 KINASE ACTIVATION IN VERTEBRATES, EMBO JOURNAL 10: 3331 (1991). (10.1002/j.1460-2075.1991.tb04897.x) / EMBO JOURNAL (1991)
  12. KUMAGAI, A, THE CDC25 PROTEIN CONTROLS TYROSINE DEPHOSPHORYLATION OF THE CDC2 PROTEIN IN A CELL-FREE SYSTEM, CELL 64: 903 (1991). (10.1016/0092-8674(91)90315-P) / CELL (1991)
  13. LEE, M.S., CDC25+ ENCODES A PROTEIN PHOSPHATASE THAT DEPHOSPHORYLATES P34CDC2, MOLECULAR BIOLOGY OF THE CELL 3: 73 (1992). (10.1091/mbc.3.1.73) / MOLECULAR BIOLOGY OF THE CELL (1992)
  14. LEW, D.J., ISOLATION OF 3 NOVEL HUMAN CYCLINS BY RESCUE OF G1 CYCLIN (CLN) FUNCTION IN YEAST, CELL 66: 1197 (1991). (10.1016/0092-8674(91)90042-W) / CELL (1991)
  15. LINDBERG, R.A., DUAL-SPECIFICITY PROTEIN-KINASES - WILL ANY HYDROXYL DO, TRENDS IN BIOCHEMICAL SCIENCES 17: 114 (1992). (10.1016/0968-0004(92)90248-8) / TRENDS IN BIOCHEMICAL SCIENCES (1992)
  16. 10.1016/0092-8674(91)90101-4
  17. MILLAR, JBA, P80CDC25 MITOTIC INDUCER IS THE TYROSINE PHOSPHATASE THAT ACTIVATES P34CDC2 KINASE IN FISSION YEAST, EMBO JOURNAL 10: 4301 (1991). (10.1002/j.1460-2075.1991.tb05008.x) / EMBO JOURNAL (1991)
  18. MURRAY, A.W., CELL BIOLOGY - THE CELL-CYCLE AS A CDC2 CYCLE, NATURE 342: 14 (1989). (10.1038/342014a0) / NATURE (1989)
  19. 10.1038/344503a0
  20. PARKER, L.L., CYCLIN PROMOTES THE TYROSINE PHOSPHORYLATION OF P34CDC2 IN A WEE1+ DEPENDENT MANNER, EMBO JOURNAL 10: 1255 (1991). (10.1002/j.1460-2075.1991.tb08067.x) / EMBO JOURNAL (1991)
  21. PARKER, L.L., P107(WEE1) IS A DUAL-SPECIFICITY KINASE THAT PHOSPHORYLATES-P34(CDC2) ON TYROSINE-15, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 89: 2917 (1992). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1992)
  22. PARKER L.L. unpublished data.
  23. PINES, J, NEW BIOL 2: 389 (1990). / NEW BIOL (1990)
  24. SADHU, K, HUMAN HOMOLOG OF FISSION YEAST CDC25 MITOTIC INDUCER IS PREDOMINANTLY EXPRESSED IN G2, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 87: 5139 (1990). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1990)
  25. SOLOMON, M.J., ROLE OF PHOSPHORYLATION IN P34CDC2 ACTIVATION - IDENTIFICATION OF AN ACTIVATING KINASE, MOLECULAR BIOLOGY OF THE CELL 3: 13 (1992). (10.1091/mbc.3.1.13) / MOLECULAR BIOLOGY OF THE CELL (1992)
  26. 10.1038/351242a0
  27. XIONG, Y, CELL 65: 691 (1991). (10.1016/0092-8674(91)90100-D) / CELL (1991)
Dates
Type When
Created 18 years, 10 months ago (Oct. 5, 2006, 7:03 p.m.)
Deposited 1 year, 7 months ago (Jan. 10, 2024, 11:04 p.m.)
Indexed 1 week, 1 day ago (Aug. 24, 2025, 7:06 p.m.)
Issued 32 years, 11 months ago (Sept. 25, 1992)
Published 32 years, 11 months ago (Sept. 25, 1992)
Published Print 32 years, 11 months ago (Sept. 25, 1992)
Funders 0

None

@article{Parker_1992, title={Inactivation of the p34 cdc2 -Cyclin B Complex by the Human WEE1 Tyrosine Kinase}, volume={257}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1384126}, DOI={10.1126/science.1384126}, number={5078}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Parker, Laura L. and Piwnica-Worms, Helen}, year={1992}, month=sep, pages={1955–1957} }