A PKC-mediated backup mechanism of the MXXCW motif-linked switch for initiating tyrosine kinase activities.
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.
Takeda
Kozue
K
Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
Kawamoto
Yoshiyuki
Y
Okuno
Yusuke
Y
Kato
Masashi
M
Takahashi
Masahide
M
Suzuki
Haruhiko
H
Isobe
Kenichi
K
Nakashima
Izumi
I
D020816:Amino Acid Motifs / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics*; D000818:Animals; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D011493:Protein Kinase C / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*
D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C