Tob, a novel protein that interacts with p185erbB2, is associated with anti-proliferative activity.
We have molecularly cloned a cDNA for a novel protein termed Tob (Transducer of ErbB-2) that interacts with the c-erbB-2 gene product p185erbB2. Nucleotide sequencing reveals that the Tob protein is a 45 kDa protein that does not contain either SH2 (Src Homology 2) or SH3 domain but is homologous to the previously characterized anti-proliferative gene product BTG-1 at its amino-terminal half. The carboxyl-terminal half of Tob is characterized by the presence of a sequence rich in proline and glutamine and shows no homology to known proteins. Like BTG-1, exogenously expressed Tob is able to suppress growth of NIH3T3 cells, but the growth suppression is hampered by the presence of kinase-active p185erbB2. By using the GST-Tob protein that contains either full length or amino-terminal half of Tob, we show that the carboxyl-terminal half of Tob is relevant to its interaction with p185erbB2. Furthermore, we could co-immunoprecipitate the Tob protein with anti-ErbB-2 antibody, and reciprocally the p185erbB2 with anti-Tob antibodies. These data suggest that p185erbB2 negatively regulates the Tob-mediated anti-proliferative pathway through its interaction with Tob, resulting possibly in growth stimulation by p185erbB2. Finally, expression of the Tob mRNA is observed in various cell types and is not correlated with expression of c-erbB-2, suggesting that other receptor-type protein-tyrosine kinases are also involved in the Tob-mediated regulation of cell growth.
Matsuda
S
S
Department of Oncology, University of Tokyo, Japan.
Kawamura-Tsuzuku
J
J
Ohsugi
M
M
Yoshida
M
M
Emi
M
M
Nakamura
Y
Y
Onda
M
M
Yoshida
Y
Y
Nishiyama
A
A
Yamamoto
T
T
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D002455:Cell Division; D002460:Cell Line; D002522:Chlorocebus aethiops; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D003001:Cloning, Molecular; D005982:Glutathione Transferase / Q000096:biosynthesis; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics; D010957:Plasmids; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D025521:Tumor Suppressor Proteins; D018909:src Homology Domains
D002352:Carrier Proteins; D005982:Glutathione Transferase; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins; C489552:Btg1 protein, mouse; C098669:TOB1 protein, human; C490903:Tob1 protein, mouse; C074086:BTG1 protein, human