Structure - Activity relationship within a series of degradation products of tautomycin

Uichi Nishiyama, Makoto Ubukata, Junji Magae, Takao Kataoka, F. Erdődi, David J. Hartshorne, Kiyoshi Isono, Kazuo Nagai, Hiroyuki Osada

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Tautomycin, a protein serine/threonine phosphatase inhibitor, was chemically degraded, and five derivatives were investigated for their biological activities. None of them exerted any inhibitory effects on the activity of protein phosphatase types 1 and 2A. However, one derivative, named TM2a, induced a significant morphological change (bleb-formation) of human myeloid leukemia K562 cells. TM2b, the trimethyl ester of TM2, did not induce bleb-formation. Thus, the maleic anhydride structure played an important role in the biological activity. The biological properties of TM2a toward K562 cells resembled those of a phorbol ester, rather than of tautomycin. The phorbol ester-induced bleb formation was abrogated by a non-specific inhibitor of protein kinases, staurosporine, and by an inhibitor of protein kinase C (PKC), H-7, but TM2a-induced bleb formation was abrogated only by staurosporine. Enhanced phosphorylation of the two proteins was observed after their exposure to TM2a. This suggest that the effect was not due to any inhibition of protein phosphatase 1 or 2A, but rather to the activation of an unidentified kinase, possibly of the PKC family, or to inhibition of a protein phosphatase other than type 1 or 2A.

Original languageEnglish
Pages (from-to)103-107
Number of pages5
JournalBioscience, Biotechnology and Biochemistry
Volume60
Issue number1
Publication statusPublished - 1996

Fingerprint

Protein Phosphatase 1
Protein Phosphatase 2
phosphoprotein phosphatase
Staurosporine
Phosphoprotein Phosphatases
Phorbol Esters
structure-activity relationships
Blister
Structure-Activity Relationship
Bioactivity
esters
protein kinase C
Maleic Anhydrides
Derivatives
Proteins
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
Degradation
Phosphorylation
degradation
K562 Cells

Keywords

  • Bleb formation
  • Protein phosphatase
  • Tautomycin; structure-activity relationship

ASJC Scopus subject areas

  • Food Science
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Biotechnology
  • Chemistry (miscellaneous)
  • Applied Microbiology and Biotechnology
  • Bioengineering

Cite this

Nishiyama, U., Ubukata, M., Magae, J., Kataoka, T., Erdődi, F., Hartshorne, D. J., ... Osada, H. (1996). Structure - Activity relationship within a series of degradation products of tautomycin. Bioscience, Biotechnology and Biochemistry, 60(1), 103-107.

Structure - Activity relationship within a series of degradation products of tautomycin. / Nishiyama, Uichi; Ubukata, Makoto; Magae, Junji; Kataoka, Takao; Erdődi, F.; Hartshorne, David J.; Isono, Kiyoshi; Nagai, Kazuo; Osada, Hiroyuki.

In: Bioscience, Biotechnology and Biochemistry, Vol. 60, No. 1, 1996, p. 103-107.

Research output: Contribution to journalArticle

Nishiyama, U, Ubukata, M, Magae, J, Kataoka, T, Erdődi, F, Hartshorne, DJ, Isono, K, Nagai, K & Osada, H 1996, 'Structure - Activity relationship within a series of degradation products of tautomycin', Bioscience, Biotechnology and Biochemistry, vol. 60, no. 1, pp. 103-107.
Nishiyama, Uichi ; Ubukata, Makoto ; Magae, Junji ; Kataoka, Takao ; Erdődi, F. ; Hartshorne, David J. ; Isono, Kiyoshi ; Nagai, Kazuo ; Osada, Hiroyuki. / Structure - Activity relationship within a series of degradation products of tautomycin. In: Bioscience, Biotechnology and Biochemistry. 1996 ; Vol. 60, No. 1. pp. 103-107.
@article{2d32a2abbc2443b09ca0ab0e141c6bbc,
title = "Structure - Activity relationship within a series of degradation products of tautomycin",
abstract = "Tautomycin, a protein serine/threonine phosphatase inhibitor, was chemically degraded, and five derivatives were investigated for their biological activities. None of them exerted any inhibitory effects on the activity of protein phosphatase types 1 and 2A. However, one derivative, named TM2a, induced a significant morphological change (bleb-formation) of human myeloid leukemia K562 cells. TM2b, the trimethyl ester of TM2, did not induce bleb-formation. Thus, the maleic anhydride structure played an important role in the biological activity. The biological properties of TM2a toward K562 cells resembled those of a phorbol ester, rather than of tautomycin. The phorbol ester-induced bleb formation was abrogated by a non-specific inhibitor of protein kinases, staurosporine, and by an inhibitor of protein kinase C (PKC), H-7, but TM2a-induced bleb formation was abrogated only by staurosporine. Enhanced phosphorylation of the two proteins was observed after their exposure to TM2a. This suggest that the effect was not due to any inhibition of protein phosphatase 1 or 2A, but rather to the activation of an unidentified kinase, possibly of the PKC family, or to inhibition of a protein phosphatase other than type 1 or 2A.",
keywords = "Bleb formation, Protein phosphatase, Tautomycin; structure-activity relationship",
author = "Uichi Nishiyama and Makoto Ubukata and Junji Magae and Takao Kataoka and F. Erdődi and Hartshorne, {David J.} and Kiyoshi Isono and Kazuo Nagai and Hiroyuki Osada",
year = "1996",
language = "English",
volume = "60",
pages = "103--107",
journal = "Bioscience, Biotechnology and Biochemistry",
issn = "0916-8451",
publisher = "Japan Society for Bioscience Biotechnology and Agrochemistry",
number = "1",

}

TY - JOUR

T1 - Structure - Activity relationship within a series of degradation products of tautomycin

AU - Nishiyama, Uichi

AU - Ubukata, Makoto

AU - Magae, Junji

AU - Kataoka, Takao

AU - Erdődi, F.

AU - Hartshorne, David J.

AU - Isono, Kiyoshi

AU - Nagai, Kazuo

AU - Osada, Hiroyuki

PY - 1996

Y1 - 1996

N2 - Tautomycin, a protein serine/threonine phosphatase inhibitor, was chemically degraded, and five derivatives were investigated for their biological activities. None of them exerted any inhibitory effects on the activity of protein phosphatase types 1 and 2A. However, one derivative, named TM2a, induced a significant morphological change (bleb-formation) of human myeloid leukemia K562 cells. TM2b, the trimethyl ester of TM2, did not induce bleb-formation. Thus, the maleic anhydride structure played an important role in the biological activity. The biological properties of TM2a toward K562 cells resembled those of a phorbol ester, rather than of tautomycin. The phorbol ester-induced bleb formation was abrogated by a non-specific inhibitor of protein kinases, staurosporine, and by an inhibitor of protein kinase C (PKC), H-7, but TM2a-induced bleb formation was abrogated only by staurosporine. Enhanced phosphorylation of the two proteins was observed after their exposure to TM2a. This suggest that the effect was not due to any inhibition of protein phosphatase 1 or 2A, but rather to the activation of an unidentified kinase, possibly of the PKC family, or to inhibition of a protein phosphatase other than type 1 or 2A.

AB - Tautomycin, a protein serine/threonine phosphatase inhibitor, was chemically degraded, and five derivatives were investigated for their biological activities. None of them exerted any inhibitory effects on the activity of protein phosphatase types 1 and 2A. However, one derivative, named TM2a, induced a significant morphological change (bleb-formation) of human myeloid leukemia K562 cells. TM2b, the trimethyl ester of TM2, did not induce bleb-formation. Thus, the maleic anhydride structure played an important role in the biological activity. The biological properties of TM2a toward K562 cells resembled those of a phorbol ester, rather than of tautomycin. The phorbol ester-induced bleb formation was abrogated by a non-specific inhibitor of protein kinases, staurosporine, and by an inhibitor of protein kinase C (PKC), H-7, but TM2a-induced bleb formation was abrogated only by staurosporine. Enhanced phosphorylation of the two proteins was observed after their exposure to TM2a. This suggest that the effect was not due to any inhibition of protein phosphatase 1 or 2A, but rather to the activation of an unidentified kinase, possibly of the PKC family, or to inhibition of a protein phosphatase other than type 1 or 2A.

KW - Bleb formation

KW - Protein phosphatase

KW - Tautomycin; structure-activity relationship

UR - http://www.scopus.com/inward/record.url?scp=0029678823&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029678823&partnerID=8YFLogxK

M3 - Article

C2 - 8824829

AN - SCOPUS:0029678823

VL - 60

SP - 103

EP - 107

JO - Bioscience, Biotechnology and Biochemistry

JF - Bioscience, Biotechnology and Biochemistry

SN - 0916-8451

IS - 1

ER -