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A PKC‐mediated backup mechanism of the MXXCW motif‐linked switch for initiating tyrosine kinase activities
Author(s) -
Takeda Kozue,
Kawamoto Yoshiyuki,
Okuno Yusuke,
Kato Masashi,
Takahashi Masahide,
Suzuki Haruhiko,
Isobe Kenichi,
Nakashima Izumi
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.01.005
Subject(s) - threonine , serine , tyrosine , phosphorylation , protein kinase c , tyrosine kinase , mutant , cysteine , biochemistry , kinase , tyrosine phosphorylation , chemistry , microbiology and biotechnology , biology , signal transduction , enzyme , gene
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.