TY - JOUR
T1 - Identification of AF-6 and Canoe as putative targets for Ras
AU - Kuriyama, Masamitsu
AU - Harada, Naozumi
AU - Kuroda, Shinya
AU - Yamamoto, Takaharu
AU - Nakafuku, Masato
AU - Iwamatsu, Akihiro
AU - Yamamoto, Daisuke
AU - Prasad, Raj
AU - Croce, Carlo
AU - Canaani, Eli
AU - Kaibuchi, Kozo
PY - 1996/1/12
Y1 - 1996/1/12
N2 - Ras (Ha-Ras, Ki-Ras, N-Ras) is implicated in the regulation of various cell functions such as gene expression and cell proliferation downstream from specific extracellular signals. Here, we partially purified a Ras-interacting protein with molecular mass of about 180 kDa (p180) from bovine brain membrane extract by glutathione S-transferase (GST)-Ha-Ras affinity column chromatography. This protein bound to the GTPγS (guanosine 5'-(3-O- thio)triphosphate, a nonhydrolyzable GTP analog)-GST-Ha-Ras affinity column but not to those containing GDP·GST-Ha-Ras or GTPγS·GST-Ha-Ras with a mutation in the effector domain (Ha-Ras(A38)). The amino acid sequences of the peptides derived from p180 were almost identical to those of human AF-6 that is identified as the fusion partner of the ALL-1 protein. The ALL-1/AF- 6 chimeric protein is the critical product of the t (6:11) abnormality associated with some human leukemia. AF-6 has a GLGF/Dlg homology repeat (DHR) motif and shows a high degree of sequence similarity with Drosophila Canoe, which is assumed to function downstream from Notch in a common developmental pathway. The recombinant N-terminal domain of AF-6 and Canoe specifically interacted with GTPγS·GST-Ha-Ras. The known Ras target c-Raf- 1 inhibited the interaction of AF-6 with GTPγS·GST-Ha-Ras. These results indicate that AF-6 and Canoe are putative targets for Ras.
AB - Ras (Ha-Ras, Ki-Ras, N-Ras) is implicated in the regulation of various cell functions such as gene expression and cell proliferation downstream from specific extracellular signals. Here, we partially purified a Ras-interacting protein with molecular mass of about 180 kDa (p180) from bovine brain membrane extract by glutathione S-transferase (GST)-Ha-Ras affinity column chromatography. This protein bound to the GTPγS (guanosine 5'-(3-O- thio)triphosphate, a nonhydrolyzable GTP analog)-GST-Ha-Ras affinity column but not to those containing GDP·GST-Ha-Ras or GTPγS·GST-Ha-Ras with a mutation in the effector domain (Ha-Ras(A38)). The amino acid sequences of the peptides derived from p180 were almost identical to those of human AF-6 that is identified as the fusion partner of the ALL-1 protein. The ALL-1/AF- 6 chimeric protein is the critical product of the t (6:11) abnormality associated with some human leukemia. AF-6 has a GLGF/Dlg homology repeat (DHR) motif and shows a high degree of sequence similarity with Drosophila Canoe, which is assumed to function downstream from Notch in a common developmental pathway. The recombinant N-terminal domain of AF-6 and Canoe specifically interacted with GTPγS·GST-Ha-Ras. The known Ras target c-Raf- 1 inhibited the interaction of AF-6 with GTPγS·GST-Ha-Ras. These results indicate that AF-6 and Canoe are putative targets for Ras.
UR - https://www.scopus.com/pages/publications/13344281006
UR - https://www.scopus.com/pages/publications/13344281006#tab=citedBy
U2 - 10.1074/jbc.271.2.607
DO - 10.1074/jbc.271.2.607
M3 - Article
C2 - 8557659
AN - SCOPUS:13344281006
SN - 0021-9258
VL - 271
SP - 607
EP - 610
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 2
ER -