Elevated Expression of RGS19 Impairs the Responsiveness of Stress-activated Protein Kinases to Serum

Overview

Journal Mol Cell Biochem

Publisher Springer

Specialty Biochemistry

Date 2011 Nov 3

PMID 22045062

Citations 1

Authors

Angel K C Ip

Prudence H Tso

Maggie M K Lee

Yung H Wong

Affiliations

Soon will be listed here.

Abstract

Regulators of G protein signaling (RGS proteins) serve as GTPase activating proteins for the signal transducing Gα subunits. RGS19, also known as Gα-interacting protein (GAIP), has been shown to subserve other functions such as the regulation of macroautophagy and growth factor signaling. We have recently demonstrated that the expression of RGS19 in human embryonic kidney (HEK) 293 cells resulted in the disruption of serum-induced mitogenic response along the classical Ras/Raf/MEK/ERK pathway. Here, we further examined the effect of RGS19 expression on the stress-activated protein kinases (SAPKs). Both c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) became non-responsive to serum in 293/RGS19 cells, yet the two SAPKs responded to UV irradiation or osmotic stress induced by sorbitol. Kinases upstream of JNK and p38 MAPK, including MKK3/6, MKK4, and MLK3, also failed to respond to serum stimulation in 293/RGS19 cells. Serum-induced activation of the small GTPases Rac1 and Cdc42 was similarly suppressed in these cells. Our results indicate that elevated expression of RGS19 can severely disrupt the regulation of MAPKs by small GTPases.

Citing Articles

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References

Zhang X, Gillespie S, Hersey P . Staurosporine induces apoptosis of melanoma by both caspase-dependent and -independent apoptotic pathways. Mol Cancer Ther. 2004; 3(2):187-97. View

Willard M, Willard F, Li X, Cappell S, Snider W, Siderovski D . Selective role for RGS12 as a Ras/Raf/MEK scaffold in nerve growth factor-mediated differentiation. EMBO J. 2007; 26(8):2029-40. PMC: 1852785. DOI: 10.1038/sj.emboj.7601659. View

Takagaki K, Satoh T, Tanuma N, Masuda K, Takekawa M, Shima H . Characterization of a novel low-molecular-mass dual-specificity phosphatase-3 (LDP-3) that enhances activation of JNK and p38. Biochem J. 2004; 383(Pt. 3):447-55. PMC: 1133737. DOI: 10.1042/BJ20040498. View

Tso P, Yung L, Wang Y, Wong Y . RGS19 stimulates cell proliferation by deregulating cell cycle control and enhancing Akt signaling. Cancer Lett. 2011; 309(2):199-208. DOI: 10.1016/j.canlet.2011.06.002. View

van Hennik P, Ten Klooster J, Halstead J, Voermans C, Anthony E, Divecha N . The C-terminal domain of Rac1 contains two motifs that control targeting and signaling specificity. J Biol Chem. 2003; 278(40):39166-75. DOI: 10.1074/jbc.M307001200. View

Tso P, Wang Y, Wong S, Poon L, Chan A, Wong Y . RGS19 enhances cell proliferation through its C-terminal PDZ motif. Cell Signal. 2010; 22(11):1700-7. DOI: 10.1016/j.cellsig.2010.06.010. View

Wang J, Wu W, Cerione R . Cdc42 and Ras cooperate to mediate cellular transformation by intersectin-L. J Biol Chem. 2005; 280(24):22883-91. DOI: 10.1074/jbc.M414375200. View

Willars G . Mammalian RGS proteins: multifunctional regulators of cellular signalling. Semin Cell Dev Biol. 2006; 17(3):363-76. DOI: 10.1016/j.semcdb.2006.03.005. View

Dhillon A, Hagan S, Rath O, Kolch W . MAP kinase signalling pathways in cancer. Oncogene. 2007; 26(22):3279-90. DOI: 10.1038/sj.onc.1210421. View

10.

Appleton C, James C, Beier F . Regulator of G-protein signaling (RGS) proteins differentially control chondrocyte differentiation. J Cell Physiol. 2006; 207(3):735-45. DOI: 10.1002/jcp.20615. View

11.

Perdiguero E, Ruiz-Bonilla V, Gresh L, Hui L, Ballestar E, Sousa-Victor P . Genetic analysis of p38 MAP kinases in myogenesis: fundamental role of p38alpha in abrogating myoblast proliferation. EMBO J. 2007; 26(5):1245-56. PMC: 1817635. DOI: 10.1038/sj.emboj.7601587. View

12.

Fu J, Yang Z, Wei J, Han J, Gu J . Nuclear protein NP60 regulates p38 MAPK activity. J Cell Sci. 2005; 119(Pt 1):115-23. DOI: 10.1242/jcs.02699. View

13.

Glaven J, Whitehead I, Bagrodia S, Kay R, Cerione R . The Dbl-related protein, Lfc, localizes to microtubules and mediates the activation of Rac signaling pathways in cells. J Biol Chem. 1999; 274(4):2279-85. DOI: 10.1074/jbc.274.4.2279. View

14.

Coso O, Chiariello M, Yu J, Teramoto H, Crespo P, Xu N . The small GTP-binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signaling pathway. Cell. 1995; 81(7):1137-46. DOI: 10.1016/s0092-8674(05)80018-2. View

15.

Liu A, Lo R, Lee M, Wang Y, Yeung W, Ho M . Galpha16 activates Ras by forming a complex with tetratricopeptide repeat 1 (TPR1) and Son of Sevenless (SOS). Cell Signal. 2010; 22(10):1448-58. DOI: 10.1016/j.cellsig.2010.05.013. View

16.

Liu Z, Chatterjee T, Fisher R . RGS6 interacts with SCG10 and promotes neuronal differentiation. Role of the G gamma subunit-like (GGL) domain of RGS6. J Biol Chem. 2002; 277(40):37832-9. DOI: 10.1074/jbc.M205908200. View

17.

Siderovski D, Willard F . The GAPs, GEFs, and GDIs of heterotrimeric G-protein alpha subunits. Int J Biol Sci. 2005; 1(2):51-66. PMC: 1142213. DOI: 10.7150/ijbs.1.51. View

18.

Matsuo N, Terao M, Nabeshima Y, Hoshino M . Roles of STEF/Tiam1, guanine nucleotide exchange factors for Rac1, in regulation of growth cone morphology. Mol Cell Neurosci. 2003; 24(1):69-81. DOI: 10.1016/s1044-7431(03)00122-2. View

19.

Penzes P, Johnson R, Sattler R, Zhang X, Huganir R, Kambampati V . The neuronal Rho-GEF Kalirin-7 interacts with PDZ domain-containing proteins and regulates dendritic morphogenesis. Neuron. 2001; 29(1):229-42. DOI: 10.1016/s0896-6273(01)00193-3. View

20.

Pruitt W, Karnoub A, Rakauskas A, Guipponi M, Antonarakis S, Kurakin A . Role of the pleckstrin homology domain in intersectin-L Dbl homology domain activation of Cdc42 and signaling. Biochim Biophys Acta. 2003; 1640(1):61-8. DOI: 10.1016/s0167-4889(03)00002-8. View