A PKC-mediated backup mechanism of the MXXCW motif-linked switch for initiating tyrosine kinase activities

Kozue Takeda; Yoshiyuki Kawamoto; Yusuke Okuno; Masashi Kato; Masahide Takahashi; Haruhiko Suzuki; Kenichi Isobe; Izumi Nakashima

doi:10.1016/j.febslet.2006.01.005

A PKC-mediated backup mechanism of the MXXCW motif-linked switch for initiating tyrosine kinase activities

Kozue Takeda
, Yoshiyuki Kawamoto
, Yusuke Okuno
, Masashi Kato
, Masahide Takahashi
, Haruhiko Suzuki
, Kenichi Isobe
, Izumi Nakashima

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

The cysteine in the M/IXXCW motif is conserved in all but one (threonine in place of cysteine) of the human protein tyrosine kinases (PTKs). We showed that all RET-PTC-1 mutants in which the C in this motif (C376) was replaced with glycine, lysine, threonine or serine lost their activity in vitro. However, the C376T/S mutants showed normal tyrosine phosphorylation in vivo (in cells). Further analyses reveled that protein kinase C (PKC) initiated the activities of the C376T/S mutants in cells. We conclude that the M/IXXCW motif-mediated mechanisms which initiate PTK activities are partially replaced by a PKC-mediated mechanism.

Original language	English
Pages (from-to)	839-843
Number of pages	5
Journal	FEBS Letters
Volume	580
Issue number	3
DOIs	https://doi.org/10.1016/j.febslet.2006.01.005
Publication status	Published - 06-02-2006
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/j.febslet.2006.01.005

Cite this

@article{ab0d38fae2ec4f76a6b5c84ea535251d,

title = "A PKC-mediated backup mechanism of the MXXCW motif-linked switch for initiating tyrosine kinase activities",

abstract = "The cysteine in the M/IXXCW motif is conserved in all but one (threonine in place of cysteine) of the human protein tyrosine kinases (PTKs). We showed that all RET-PTC-1 mutants in which the C in this motif (C376) was replaced with glycine, lysine, threonine or serine lost their activity in vitro. However, the C376T/S mutants showed normal tyrosine phosphorylation in vivo (in cells). Further analyses reveled that protein kinase C (PKC) initiated the activities of the C376T/S mutants in cells. We conclude that the M/IXXCW motif-mediated mechanisms which initiate PTK activities are partially replaced by a PKC-mediated mechanism.",

keywords = "Cysteine, Protein tyrosine kinase, RET, Redox",

author = "Kozue Takeda and Yoshiyuki Kawamoto and Yusuke Okuno and Masashi Kato and Masahide Takahashi and Haruhiko Suzuki and Kenichi Isobe and Izumi Nakashima",

note = "Funding Information: We thank M. Nagao and Y. Ishizaka for providing us with RET-PTC-1 cDNA. This study was supported in part by Grants-in-Aid for Scientific Research B and Scientific Research of Priority Areas from the Ministry of Education, Science, Sports and Culture of Japan.",

year = "2006",

month = feb,

day = "6",

doi = "10.1016/j.febslet.2006.01.005",

language = "English",

volume = "580",

pages = "839--843",

journal = "FEBS Letters",

issn = "0014-5793",

publisher = "John Wiley and Sons Inc.",

number = "3",

}

TY - JOUR

T1 - A PKC-mediated backup mechanism of the MXXCW motif-linked switch for initiating tyrosine kinase activities

AU - Takeda, Kozue

AU - Kawamoto, Yoshiyuki

AU - Okuno, Yusuke

AU - Kato, Masashi

AU - Takahashi, Masahide

AU - Suzuki, Haruhiko

AU - Isobe, Kenichi

AU - Nakashima, Izumi

N1 - Funding Information: We thank M. Nagao and Y. Ishizaka for providing us with RET-PTC-1 cDNA. This study was supported in part by Grants-in-Aid for Scientific Research B and Scientific Research of Priority Areas from the Ministry of Education, Science, Sports and Culture of Japan.

PY - 2006/2/6

Y1 - 2006/2/6

N2 - The cysteine in the M/IXXCW motif is conserved in all but one (threonine in place of cysteine) of the human protein tyrosine kinases (PTKs). We showed that all RET-PTC-1 mutants in which the C in this motif (C376) was replaced with glycine, lysine, threonine or serine lost their activity in vitro. However, the C376T/S mutants showed normal tyrosine phosphorylation in vivo (in cells). Further analyses reveled that protein kinase C (PKC) initiated the activities of the C376T/S mutants in cells. We conclude that the M/IXXCW motif-mediated mechanisms which initiate PTK activities are partially replaced by a PKC-mediated mechanism.

AB - The cysteine in the M/IXXCW motif is conserved in all but one (threonine in place of cysteine) of the human protein tyrosine kinases (PTKs). We showed that all RET-PTC-1 mutants in which the C in this motif (C376) was replaced with glycine, lysine, threonine or serine lost their activity in vitro. However, the C376T/S mutants showed normal tyrosine phosphorylation in vivo (in cells). Further analyses reveled that protein kinase C (PKC) initiated the activities of the C376T/S mutants in cells. We conclude that the M/IXXCW motif-mediated mechanisms which initiate PTK activities are partially replaced by a PKC-mediated mechanism.

KW - Cysteine

KW - Protein tyrosine kinase

KW - RET

KW - Redox

UR - https://www.scopus.com/pages/publications/31444451659

UR - https://www.scopus.com/pages/publications/31444451659#tab=citedBy

U2 - 10.1016/j.febslet.2006.01.005

DO - 10.1016/j.febslet.2006.01.005

M3 - Article

C2 - 16427628

AN - SCOPUS:31444451659

SN - 0014-5793

VL - 580

SP - 839

EP - 843

JO - FEBS Letters

JF - FEBS Letters

IS - 3

ER -

A PKC-mediated backup mechanism of the MXXCW motif-linked switch for initiating tyrosine kinase activities

Abstract

All Science Journal Classification (ASJC) codes

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