Gs and Gq signalings regulate hPEM-2-induced cell responses in Neuro-2a cells
Gs and Gq signalings regulate hPEM-2-induced cell responses in Neuro-2a cells
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DOI：
10.1016/j.bbrc.2011.10.047
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发表时间：
2011-11-11
影响因子：
3.1
通讯作者：
Ueda, Hiroshi
中科院分区：
文献类型：
--
作者：
Nagae, Rika;Sato, Katsuya;Ueda, Hiroshi
Dbl家族的Rho家族GTP酶特异性鸟嘌呤核苷酸交换因子通过激活Rho家族GTP酶来调节多种细胞事件，包括细胞骨架排列、信号转导和基因表达。在这项研究中，我们发现hPEM-2是Neuro-2a神经母细胞瘤细胞中G（s）和G（q）信号的下游效应子。与hPEM-2和G α s（G α（s）Q213 L）或G α（q）（G α（q）Q209 L）的GTP酶缺陷（组成型活性）突变体共表达，但不与G α亚基和G β γ亚基的其他GTP酶缺陷突变体共表达，激活血清应答元件（SRE）依赖性基因转录，已知其由Rho家族激活诱导。尽管Rac 1的显性负突变体强烈阻断G α（s）Q213 L或G α（q）Q209 L/hPEM-2激活的SRE依赖性基因转录，但Cdc 42或RhoA的那些受到轻微影响。PKA抑制剂H-89可减弱G alpha/hPEM-2激活的SRE依赖性基因转录。c-Src的显性失活突变体和Src抑制剂减弱G α（q）Q209 L/hPEM-2激活的SRE依赖性基因转录。使用hPEM-2缺失突变体的实验表明，hPEM-2的某些区域在通过G（s）和G（q）信号传导增强SRE激活中起重要作用。这些结果表明G（s）和G（q）信号分别通过PKA和c-Src调节Neuro-2a神经母细胞瘤细胞中hPEM-2的功能。(C)2011 Elsevier Inc. All rights reserved.
Rho family GTPase-specific guanine nucleotide exchange factors of the Dbl family regulate a variety of cellular events including cytoskeletal arrangement, signal transduction, and gene expression through activation of Rho family GTPases. In this study, we show that hPEM-2 is a downstream effector of G(s) and G(q) signaling in Neuro-2a neuroblastoma cells. Co-expression with hPEM-2 and GTPase-deficient (constitutively active) mutants of G alpha s (G alpha(s)Q213L) or G alpha(q) (G alpha(q)Q209L), but not other GTPase-deficient mutants of G alpha subunit and G beta gamma subunits, activated serum response element (SRE)-dependent gene transcription, which is known to be induced by Rho family activation. Although a dominant negative mutant of Rac1 strongly blocks G alpha(s)Q213L or G alpha(q)Q209L/hPEM-2 activated SRE-dependent gene transcription, those of Cdc42 or RhoA are marginally affected. A PKA inhibitor, H-89, attenuated G alpha(s)/hPEM-2-activated SRE-dependent gene transcription. And a dominant negative mutant of c-Src and an Src inhibitor attenuated G alpha(q)Q209L/hPEM-2-activated SRE-dependent gene transcription. Experiments using hPEM-2 deletion mutants indicate that some regions of hPEM-2 play an important role in enhancing SRE activation by G(s) and G(q) signalings. These results reveal that G(s) and G(q) signalings regulate hPEM-2 functions through PKA and c-Src in Neuro-2a neuroblastoma cells, respectively. (C) 2011 Elsevier Inc. All rights reserved.