Identification of B cell adaptor for PI3-kinase (BCAP) as an Abl interactor 1-regulated substrate of Abl kinases.
In previous work we showed that Abl interactor 1 (Abi-1), by linking enzyme and substrate, promotes the phosphorylation of Mammalian Enabled (Mena) by c-Abl. To determine whether this mechanism extends to other c-Abl substrates, we used the yeast two-hybrid system to search for proteins that interact with Abi-1. By screening a human leukocyte cDNA library, we identified BCAP (B-cell adaptor for phosphoinositide 3-kinase) as another Abi-1-interacting protein. Binding experiments revealed that the SH3 domain of Abi-1 and the C-terminal polyproline structure of BCAP are involved in interactions between the two. In cultured cells, Abi-1 promoted phosphorylation of BCAP not only by c-Abl but also by v-Abl. The phosphorylation sites of BCAP by c-Abl were mapped to five tyrosine residues in the C-terminal region that are well conserved in mammals. These results show that Abi-1 promotes Abl-mediated BCAP phosphorylation and suggest that Abi-1 in general coordinates kinase-substrate interactions.
Maruoka
Masahiro
M
Laboratory of Molecular Oncology, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0101, Japan.
Suzuki
Jun
J
Kawata
Shigehisa
S
Yoshida
Kayo
K
Hirao
Noriko
N
Sato
Seiichi
S
Goff
Stephen P
SP
Takeya
Tatsuo
T
Tani
Katsuko
K
Shishido
Tomoyuki
T
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D016374:Oncogene Proteins v-abl / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D016374:Oncogene Proteins v-abl; D019000:Phosphotyrosine; D016315:Proto-Oncogene Proteins c-abl