Functional roles of BCAR3 in the signaling pathways of insulin leading to DNA synthesis, membrane ruffling and GLUT4 translocation.
Breast cancer anti-estrogen resistance 3 (BCAR3) is an SH2-containing signal transducer and is implicated in tumorigenesis of breast cancer cells. In this study, we found that BCAR3 mediates the induction of ERK activation and DNA synthesis by insulin, but not by IGF-1. Specifically, the SH2 domain of BCAR3 is involved in insulin-stimulated DNA synthesis. Differential tyrosine-phosphorylated patterns of the BCAR3 immune complex were detected in insulin and IGF-1 signaling, suggesting that BCAR3 is a distinct target molecule of insulin and IGF-1 signaling. Moreover, microinjection of BCAR3 inhibitory materials inhibited membrane ruffling induced by insulin, while this did not affect insulin-mediated GLUT4 translocation. Taken together, these results demonstrated that BCAR3 plays an important role in the signaling pathways of insulin leading to cell cycle progression and cytoskeleton reorganization, but not GLUT4 translocation.
Clinical Trials Management Division, Pharmaceutical Safety Bureau, Ministry of Food and Drug Safety, Cheongwon, Chungbuk 363-700, Republic of Korea.
Myung-Ju
MJ
Oh
Sun-Ju
SJ
Yi
Hye Sung
HS
Kim
Ji-Hyun
JH
Kim
Young-Hwa
YH
Jeong
Ton
T
van Agthoven
Byung H
BH
Jhun
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D000818:Animals; D045744:Cell Line, Tumor; D004261:DNA Replication / Q000502:physiology*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C118588:BCAR3 protein, human; D051275:Glucose Transporter Type 4; D020662:Guanine Nucleotide Exchange Factors; C583557:IGF1 protein, human; D007328:Insulin; C495692:SLC2A4 protein, human; D014443:Tyrosine; D007334:Insulin-Like Growth Factor I
BCAR3; DNA synthesis; GLUT4 translocation; IGF-I; Insulin; Membrane ruffling; Microinjection