Differential signaling through p190 and p210 BCR-ABL fusion proteins revealed by interactome and phosphoproteome analysis

被引：0
作者：
J A Cutler
R Tahir
S K Sreenivasamurthy
C Mitchell
S Renuse
R S Nirujogi
A H Patil
M Heydarian
X Wong
X Wu
T-C Huang
M-S Kim
K L Reddy
A Pandey
机构：
[1] Pre-Doctoral Training Program in Human Genetics,Department of Biological Chemistry
[2] McKusick-Nathans Institute of Genetic Medicine,Division of Hematology, Department of Internal Medicine
[3] Johns Hopkins University School of Medicine,Department of Applied Chemistry
[4] Johns Hopkins University School of Medicine,Departments of Pathology and Oncology
[5] Center for Epigenetics,undefined
[6] Johns Hopkins University School of Medicine,undefined
[7] McKusick-Nathans Institute of Genetic Medicine,undefined
[8] Johns Hopkins University School of Medicine,undefined
[9] Biochemistry,undefined
[10] Cellular and Molecular Biology Graduate Program,undefined
[11] Johns Hopkins University School of Medicine,undefined
[12] Institute of Bioinformatics,undefined
[13] International Technology Park,undefined
[14] Ginkgo Bioworks,undefined
[15] Center for Proteomics Discovery,undefined
[16] Johns Hopkins University School of Medicine,undefined
[17] School of Biotechnology,undefined
[18] KIIT University,undefined
[19] Laboratory of Developmental and Regenerative Biology,undefined
[20] Institute of Medical Biology,undefined
[21] Agency for Science,undefined
[22] Technology and Research (A∗STAR),undefined
[23] National Taiwan University and National Taiwan University Cancer Center,undefined
[24] Kyung Hee University,undefined
[25] Sidney Kimmel Comprehensive Cancer Center,undefined
[26] Johns Hopkins University,undefined
[27] School of Medicine,undefined
[28] Johns Hopkins,undefined
[29] University School of Medicine,undefined
来源：
Leukemia | 2017年 / 31卷
关键词：
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Two major types of leukemogenic BCR-ABL fusion proteins are p190BCR-ABLand p210BCR-ABL. Although the two fusion proteins are closely related, they can lead to different clinical outcomes. A thorough understanding of the signaling programs employed by these two fusion proteins is necessary to explain these clinical differences. We took an integrated approach by coupling protein–protein interaction analysis using biotinylation identification with global phosphorylation analysis to investigate the differences in signaling between these two fusion proteins. Our findings suggest that p190BCR-ABL and p210BCR-ABL differentially activate important signaling pathways, such as JAK-STAT, and engage with molecules that indicate interaction with different subcellular compartments. In the case of p210BCR-ABL, we observed an increased engagement of molecules active proximal to the membrane and in the case of p190BCR-ABL, an engagement of molecules of the cytoskeleton. These differences in signaling could underlie the distinct leukemogenic process induced by these two protein variants.
引用
收藏
页码：1513 / 1524
页数：11
相关论文
共 305 条
[1]  
Score J(2010)Analysis of genomic breakpoints in p190 and p210 BCR-ABL indicate distinct mechanisms of formation Leukemia 24 1742-1750
[2]  
Calasanz MJ(2009)The function of the pleckstrin homology domain in BCR-ABL-mediated leukemogenesis Leukemia 24 226-229
[3]  
Ottman O(2011)Dasatinib as first-line treatment for adult patients with Philadelphia chromosome–positive acute lymphoblastic leukemia Blood 118 6521-6528
[4]  
Pane F(2016)First line treatment with newer tyrosine kinase inhibitors in chronic myeloid leukemia associated with deep and durable molecular response – systematic review and meta-analysis Acta Oncol 55 1077-1083
[5]  
Yeh RF(2013)Contributions of the RhoGEF activity of p210 BCR/ABL to disease progression Leukemia 27 1080-1089
[6]  
Sobrinho-Simões MA(1999)The P190, P210, and P230 forms of the BCR/ABL oncogene induce a similar chronic myeloid leukemia–like syndrome in mice but have different lymphoid leukemogenic activity J Exp Med 189 1399-1412
[7]  
Demehri S(1990)Tyrosine kinase activity and transformation potency of bcr-abl oncogene products Science 247 1079-1082
[8]  
O’Hare T(2012)Structure, regulation, signaling, and targeting of Abl kinases in cancer Genes Cancer 3 436-446
[9]  
Eide CA(2012)Molecular pathways: BCR-ABL Clin Cancer Res 18 930-937
[10]  
Smith CA(2003)Differential interaction and activation of Rho family GTPases by p210bcr-abl and p190bcr-abl Oncogene 22 6445-6454
12345678910