G protein coupled receptor signaling through the Src and Stat3 pathway: role in proliferation and transformation

被引:108
作者
Ram, PT [1 ]
Iyengar, R [1 ]
机构
[1] CUNY Mt Sinai Sch Med, Dept Pharmacol, New York, NY 10029 USA
关键词
G protein alpha subunit; Src; Stat3; transformation;
D O I
10.1038/sj.onc.1204186
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Extracellular signals when routed through signaling pathways that use heterotrimeric G proteins can engage multiple signaling pathways leading to diverse biological consequences, One locus at which signal sorting occurs is at the level of G proteins, G protein a-subunits appear to be capable of interacting with different effecters leading to engagement of distinct signaling pathways. Regulation of different pathways in turn leads to different biological outcomes, The process of neoplastic transformation is controlled to a large extent through the activation and inhibition of signaling pathways, Signaling pathways such as the Ras-MAPK, v-Src-Stat3 pathways are activated in the process of transformation. Expression of activated G alpha subunits have been shown to cause transformation of cells, While activation of the MAPK 1,2 pathway by various G alpha subunits has been reported for several years, recent studies show the activation and involvement of Src and Stat3 pathways in G alphao and G alphai mediated transformation of cells. Recent studies also suggest that both G alphai and G alphas may be able to interact with and activate Src, The activation of Src and Stat3 by G proteins has also been demonstrated by Ligand-induced activation of G protein receptors, So increasingly it is becoming clear that the Src and Stat3 pathways are potential effecters for G proteins and that they may play a role in G protein function.
引用
收藏
页码:1601 / 1606
页数:6
相关论文
共 61 条
[1]   Roles of STAT3 defined by tissue-specific gene targeting [J].
Akira, S .
ONCOGENE, 2000, 19 (21) :2607-2611
[2]   G-PROTEIN-COUPLED RECEPTOR GENES AS PROTOONCOGENES - CONSTITUTIVELY ACTIVATING MUTATION OF THE ALPHA-1B-ADRENERGIC RECEPTOR ENHANCES MITOGENESIS AND TUMORIGENICITY [J].
ALLEN, LF ;
LEFKOWITZ, RJ ;
CARON, MG ;
COTECCHIA, S .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (24) :11354-11358
[3]   Human herpesvirus KSHV encodes a constitutively active G-protein-coupled receptor linked to cell proliferation [J].
Arvanitakis, L ;
GerasRaaka, E ;
Varma, A ;
Gershengorn, MC ;
Cesarman, E .
NATURE, 1997, 385 (6614) :347-350
[4]   All in the family? New insights and questions regarding interconnectivity of Ras, Rap1 and Ral [J].
Bos, JL .
EMBO JOURNAL, 1998, 17 (23) :6776-6782
[5]   STATs in oncogenesis [J].
Bowman, T ;
Garcia, R ;
Turkson, J ;
Jove, R .
ONCOGENE, 2000, 19 (21) :2474-2488
[6]   The role of STATs in transcriptional control and their impact on cellular function [J].
Bromberg, J ;
Darnell, JE .
ONCOGENE, 2000, 19 (21) :2468-2473
[7]   Stat3 as an oncogene [J].
Bromberg, JF ;
Wrzeszczynska, MH ;
Devgan, G ;
Zhao, YX ;
Pestell, RG ;
Albanese, C ;
Darnell, JE .
CELL, 1999, 98 (03) :295-303
[8]   Stat3 activation is required for cellular transformation by v-src [J].
Bromberg, JF ;
Horvath, CM ;
Besser, D ;
Lathem, WW ;
Darnell, JE .
MOLECULAR AND CELLULAR BIOLOGY, 1998, 18 (05) :2553-2558
[9]   Regulation, substrates and functions of src [J].
Brown, MT ;
Cooper, JA .
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 1996, 1287 (2-3) :121-149
[10]   Binding of α-melanocyte-stimulating hormone to its G-protein-coupled receptor on B-lymphocytes activates the Jak/STAT pathway [J].
Buggy, JJ .
BIOCHEMICAL JOURNAL, 1998, 331 :211-216