FKBP, the binding protein for the immunosuppressive drug, FK-506, is not an inhibitor of protein kinase C activity

John Cryan, Shirley H Y Hung, Gregory Wiederrecht, Nolan H. Sigal, John Siekierka

Research output: Contribution to journalArticleResearchpeer-review

9 Citations (Scopus)

Abstract

Recently, the amino acid sequence of a 12 Kd endogenous protein inhibitor of protein kinase C (PKC-I 2) has been shown to be identical to that of the 12 KDa receptor for the immunosuppressive drug, FK-506. In view of this observation we examined the effects of recombinant and native human FKBP on protein kinase C (PKC) activity. FKBP, at molar concentrations up to 1900-fold over that of PKC, failed to inhibit PKC phosphorylation of histone H1 and failed to block the auto-phosphorylation of PKC. Interestingly, FKBP is phosphorylated by PKC in these reactions. The phosphorylation of FKBP by PKC appears to be specific since the catalytic subunit of cAMP-dependent protein kinase fails to phosphorylate the binding protein. Our results fail to support a role for FKBP as an inhibitor of protein kinase C.

Original languageEnglish
Pages (from-to)846-852
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume180
Issue number2
DOIs
StatePublished - 31 Oct 1991

Fingerprint

Tacrolimus Binding Proteins
Tacrolimus
Immunosuppressive Agents
Protein Kinase C
Carrier Proteins
Pharmaceutical Preparations
Phosphorylation
Drug Receptors
Cyclic AMP-Dependent Protein Kinases
Population Groups
Histones
Amino Acid Sequence
Catalytic Domain
Amino Acids

Cite this

@article{6b99dfef359e47a1be16eade7640d16a,
title = "FKBP, the binding protein for the immunosuppressive drug, FK-506, is not an inhibitor of protein kinase C activity",
abstract = "Recently, the amino acid sequence of a 12 Kd endogenous protein inhibitor of protein kinase C (PKC-I 2) has been shown to be identical to that of the 12 KDa receptor for the immunosuppressive drug, FK-506. In view of this observation we examined the effects of recombinant and native human FKBP on protein kinase C (PKC) activity. FKBP, at molar concentrations up to 1900-fold over that of PKC, failed to inhibit PKC phosphorylation of histone H1 and failed to block the auto-phosphorylation of PKC. Interestingly, FKBP is phosphorylated by PKC in these reactions. The phosphorylation of FKBP by PKC appears to be specific since the catalytic subunit of cAMP-dependent protein kinase fails to phosphorylate the binding protein. Our results fail to support a role for FKBP as an inhibitor of protein kinase C.",
author = "John Cryan and Hung, {Shirley H Y} and Gregory Wiederrecht and Sigal, {Nolan H.} and John Siekierka",
year = "1991",
month = "10",
day = "31",
doi = "10.1016/S0006-291X(05)81142-8",
language = "English",
volume = "180",
pages = "846--852",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "2",

}

FKBP, the binding protein for the immunosuppressive drug, FK-506, is not an inhibitor of protein kinase C activity. / Cryan, John; Hung, Shirley H Y; Wiederrecht, Gregory; Sigal, Nolan H.; Siekierka, John.

In: Biochemical and Biophysical Research Communications, Vol. 180, No. 2, 31.10.1991, p. 846-852.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - FKBP, the binding protein for the immunosuppressive drug, FK-506, is not an inhibitor of protein kinase C activity

AU - Cryan, John

AU - Hung, Shirley H Y

AU - Wiederrecht, Gregory

AU - Sigal, Nolan H.

AU - Siekierka, John

PY - 1991/10/31

Y1 - 1991/10/31

N2 - Recently, the amino acid sequence of a 12 Kd endogenous protein inhibitor of protein kinase C (PKC-I 2) has been shown to be identical to that of the 12 KDa receptor for the immunosuppressive drug, FK-506. In view of this observation we examined the effects of recombinant and native human FKBP on protein kinase C (PKC) activity. FKBP, at molar concentrations up to 1900-fold over that of PKC, failed to inhibit PKC phosphorylation of histone H1 and failed to block the auto-phosphorylation of PKC. Interestingly, FKBP is phosphorylated by PKC in these reactions. The phosphorylation of FKBP by PKC appears to be specific since the catalytic subunit of cAMP-dependent protein kinase fails to phosphorylate the binding protein. Our results fail to support a role for FKBP as an inhibitor of protein kinase C.

AB - Recently, the amino acid sequence of a 12 Kd endogenous protein inhibitor of protein kinase C (PKC-I 2) has been shown to be identical to that of the 12 KDa receptor for the immunosuppressive drug, FK-506. In view of this observation we examined the effects of recombinant and native human FKBP on protein kinase C (PKC) activity. FKBP, at molar concentrations up to 1900-fold over that of PKC, failed to inhibit PKC phosphorylation of histone H1 and failed to block the auto-phosphorylation of PKC. Interestingly, FKBP is phosphorylated by PKC in these reactions. The phosphorylation of FKBP by PKC appears to be specific since the catalytic subunit of cAMP-dependent protein kinase fails to phosphorylate the binding protein. Our results fail to support a role for FKBP as an inhibitor of protein kinase C.

UR - http://www.scopus.com/inward/record.url?scp=0025720457&partnerID=8YFLogxK

U2 - 10.1016/S0006-291X(05)81142-8

DO - 10.1016/S0006-291X(05)81142-8

M3 - Article

VL - 180

SP - 846

EP - 852

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 2

ER -