TY - JOUR
T1 - Requirement of two specific tyrosine residues for the catalytic activity of Bcr serine/threonine kinase
AU - Wu, Yun
AU - Liu, Jiaxin
AU - Arlinghaus, Ralph B.
N1 - Funding Information:
RBA is the recipient of the Hubert L Stringer Chair in Cancer Research. This work was supported by grants from NIH (CA16672 and CA65611). We thank Tammy Trlicek for assistance in manuscript preparation.
PY - 1998/1/8
Y1 - 1998/1/8
N2 - Bcr is a novel serine/threonine protein kinase that is believed to require two cysteine pairs for activity. Tyrosine phosphorylated Bcr has dramatically reduced kinase activity, and tyrosine 360 of Bcr, which is one of the sites of phosphorylation by the Bcr-Abl oncoprotein, is required for transkinase activity. Results presented here indicate that Bcr tyrosine 328 is also phosphorylated within Bcr-Abl expressing cells and is required for Bcr's serine/threonine kinase activity. Bcr Y328F, like Bcr Y360F, had defective transkinase activity but can autophosphorylate. However, the Y328F/Y360F double mutant of Bcr is defective in both trans- and autokinase activities. Taken together with the kinase inhibitory effects of tyrosine phosphorylation of Bcr by Bcr-Abl, our studies with tyrosine to phenylalanine Bcr mutants indicate that the hydroxyl residues of tyrosines 328 and 360 play crucial roles in Bcr's kinase activity.
AB - Bcr is a novel serine/threonine protein kinase that is believed to require two cysteine pairs for activity. Tyrosine phosphorylated Bcr has dramatically reduced kinase activity, and tyrosine 360 of Bcr, which is one of the sites of phosphorylation by the Bcr-Abl oncoprotein, is required for transkinase activity. Results presented here indicate that Bcr tyrosine 328 is also phosphorylated within Bcr-Abl expressing cells and is required for Bcr's serine/threonine kinase activity. Bcr Y328F, like Bcr Y360F, had defective transkinase activity but can autophosphorylate. However, the Y328F/Y360F double mutant of Bcr is defective in both trans- and autokinase activities. Taken together with the kinase inhibitory effects of tyrosine phosphorylation of Bcr by Bcr-Abl, our studies with tyrosine to phenylalanine Bcr mutants indicate that the hydroxyl residues of tyrosines 328 and 360 play crucial roles in Bcr's kinase activity.
KW - Bcr serine/threonine kinase
KW - Bcr tyrosine residues
KW - Inhibition of Bcr serine kinase by Bcr-Abl
KW - Kinase role of Bcr tyrosines 328 and 360
KW - Tyrosine phosphorylation of Bcr
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U2 - 10.1038/sj.onc.1201524
DO - 10.1038/sj.onc.1201524
M3 - Article
C2 - 9467953
AN - SCOPUS:0032495554
SN - 0950-9232
VL - 16
SP - 141
EP - 146
JO - Oncogene
JF - Oncogene
IS - 1
ER -