Involvement of an SHP-2-Rho Small G Protein Pathway in Hepatocyte Growth Factor/scatter Factor-induced Cell Scattering

Overview

Journal Mol Biol Cell

Specialties Cell Biology
Molecular Biology

Date 2000 Aug 10

PMID 10930454

Citations 45

Authors

A Kodama

T Matozaki

A Fukuhara

M Kikyo

M Ichihashi

Y Takai

Affiliations

Soon will be listed here.

Abstract

Hepatocyte growth factor/scatter factor (HGF/SF) induces cell scattering through the tyrosine kinase-type HGF/SF receptor c-Met. We have previously shown that Rho small G protein (Rho) is involved in the HGF/SF-induced scattering of Madin-Darby canine kidney (MDCK) cells by regulating at least the assembly and disassembly of stress fibers and focal adhesions, but it remains unknown how c-Met regulates Rho activity. We have found here a novel signaling pathway of c-Met consisting of SHP-2-Rho that regulates the assembly and disassembly of stress fibers and focal adhesions in MDCK cells. SHP-2 is a protein-tyrosine phosphatase that contains src homology-2 domains. Expression of a dominant negative mutant of SHP-2 (SHP-2-C/S) markedly increased the formation of stress fibers and focal adhesions in MDCK cells and inhibited their scattering. C3, a Clostridium botulinum ADP-ribosyltransferase, and Y-27632, a specific inhibitor for ROCK, reversed the stimulatory effect of SHP-2-C/S on stress fiber formation and the inhibitory effect on cell scattering. Vav2 is a GDP/GTP exchange protein for Rho. Expression of a dominant negative mutant of Vav2 blocked the stimulatory effect of SHP-2-C/S on stress fiber formation. Conversely, expression of mutants of Vav2 that increased stress fiber formation inhibited HGF/SF-induced cell scattering. These results indicate that SHP-2 physiologically modulates the activity of Rho to form stress fibers and focal adhesions and thereby regulates HGF/SF-induced cell scattering. In addition, Vav2 may be involved in the SHP-2-Rho pathway.

Citing Articles

Protein tyrosine phosphatase 11 acts through RhoA/ROCK to regulate eosinophil accumulation in the allergic airway.

Xu C, Wu X, Lu M, Tang L, Yao H, Wang J FASEB J. 2019; 33(11):11706-11720.

PMID: 31361966 PMC: 6902720. DOI: 10.1096/fj.201900698R.

Epithelial polarization in 3D matrix requires DDR1 signaling to regulate actomyosin contractility.

Sogaard P, Ito N, Sato N, Fujita Y, Matter K, Itoh Y Life Sci Alliance. 2019; 2(1).

PMID: 30760555 PMC: 6374992. DOI: 10.26508/lsa.201800276.

Tyrosine dephosphorylated cortactin downregulates contractility at the epithelial zonula adherens through SRGAP1.

Liang X, Budnar S, Gupta S, Verma S, Han S, Hill M Nat Commun. 2017; 8(1):790.

PMID: 28983097 PMC: 5629210. DOI: 10.1038/s41467-017-00797-w.

Hepatocyte Growth Factor Isoforms in Tissue Repair, Cancer, and Fibrotic Remodeling.

Mungunsukh O, McCart E, Day R Biomedicines. 2017; 2(4):301-326.

PMID: 28548073 PMC: 5344272. DOI: 10.3390/biomedicines2040301.

Physiological Signaling and Structure of the HGF Receptor MET.

Baldanzi G, Graziani A Biomedicines. 2017; 3(1):1-31.

PMID: 28536396 PMC: 5344233. DOI: 10.3390/biomedicines3010001.

References

Manes S, Mira E, Zhao Z, Lacalle R, Martinez-A C . Concerted activity of tyrosine phosphatase SHP-2 and focal adhesion kinase in regulation of cell motility. Mol Cell Biol. 1999; 19(4):3125-35. PMC: 84106. DOI: 10.1128/MCB.19.4.3125. View

Noguchi T, Matozaki T, Fujioka Y, Yamao T, Tsuda M, Takada T . Characterization of a 115-kDa protein that binds to SH-PTP2, a protein-tyrosine phosphatase with Src homology 2 domains, in Chinese hamster ovary cells. J Biol Chem. 1996; 271(44):27652-8. DOI: 10.1074/jbc.271.44.27652. View

Qi J, Ito N, Claesson-Welsh L . Tyrosine phosphatase SHP-2 is involved in regulation of platelet-derived growth factor-induced migration. J Biol Chem. 1999; 274(20):14455-63. DOI: 10.1074/jbc.274.20.14455. View

Ridley A, Allen W, Peppelenbosch M, Jones G . Rho family proteins and cell migration. Biochem Soc Symp. 1999; 65:111-23. View

Kodama A, Takaishi K, Nakano K, Nishioka H, Takai Y . Involvement of Cdc42 small G protein in cell-cell adhesion, migration and morphology of MDCK cells. Oncogene. 1999; 18(27):3996-4006. DOI: 10.1038/sj.onc.1202773. View

Kamei T, Matozaki T, Sakisaka T, Kodama A, Yokoyama S, Peng Y . Coendocytosis of cadherin and c-Met coupled to disruption of cell-cell adhesion in MDCK cells--regulation by Rho, Rac and Rab small G proteins. Oncogene. 1999; 18(48):6776-84. DOI: 10.1038/sj.onc.1203114. View

Abe K, Rossman K, Liu B, Ritola K, Chiang D, Campbell S . Vav2 is an activator of Cdc42, Rac1, and RhoA. J Biol Chem. 2000; 275(14):10141-9. DOI: 10.1074/jbc.275.14.10141. View

Burridge K, Mangeat P . An interaction between vinculin and talin. Nature. 1984; 308(5961):744-6. DOI: 10.1038/308744a0. View

Kikuchi A, Yamamoto K, Fujita T, Takai Y . ADP-ribosylation of the bovine brain rho protein by botulinum toxin type C1. J Biol Chem. 1988; 263(31):16303-8. View

10.

Narumiya S, Sekine A, Fujiwara M . Substrate for botulinum ADP-ribosyltransferase, Gb, has an amino acid sequence homologous to a putative rho gene product. J Biol Chem. 1988; 263(33):17255-7. View

11.

Bottaro D, Rubin J, Faletto D, Chan A, Kmiecik T, Woude G . Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science. 1991; 251(4995):802-4. DOI: 10.1126/science.1846706. View

12.

Stoker M, Gherardi E . Regulation of cell movement: the motogenic cytokines. Biochim Biophys Acta. 1991; 1072(1):81-102. DOI: 10.1016/0304-419x(91)90008-9. View

13.

Naldini L, Vigna E, Narsimhan R, Gaudino G, Zarnegar R, Michalopoulos G . Hepatocyte growth factor (HGF) stimulates the tyrosine kinase activity of the receptor encoded by the proto-oncogene c-MET. Oncogene. 1991; 6(4):501-4. View

14.

Mayer B, Jackson P, Van Etten R, Baltimore D . Point mutations in the abl SH2 domain coordinately impair phosphotyrosine binding in vitro and transforming activity in vivo. Mol Cell Biol. 1992; 12(2):609-18. PMC: 364250. DOI: 10.1128/mcb.12.2.609-618.1992. View

15.

Waksman G, Kominos D, Robertson S, Pant N, Baltimore D, Birge R . Crystal structure of the phosphotyrosine recognition domain SH2 of v-src complexed with tyrosine-phosphorylated peptides. Nature. 1992; 358(6388):646-53. DOI: 10.1038/358646a0. View

16.

Backer J, Myers Jr M, Shoelson S, Chin D, Sun X, Miralpeix M . Phosphatidylinositol 3'-kinase is activated by association with IRS-1 during insulin stimulation. EMBO J. 1992; 11(9):3469-79. PMC: 556882. DOI: 10.1002/j.1460-2075.1992.tb05426.x. View

17.

Takaishi K, Kikuchi A, Kuroda S, Kotani K, Sasaki T, Takai Y . Involvement of rho p21 and its inhibitory GDP/GTP exchange protein (rho GDI) in cell motility. Mol Cell Biol. 1993; 13(1):72-9. PMC: 358886. DOI: 10.1128/mcb.13.1.72-79.1993. View

18.

Eck M, Shoelson S, Harrison S . Recognition of a high-affinity phosphotyrosyl peptide by the Src homology-2 domain of p56lck. Nature. 1993; 362(6415):87-91. DOI: 10.1038/362087a0. View

19.

Weidner K, Sachs M, Birchmeier W . The Met receptor tyrosine kinase transduces motility, proliferation, and morphogenic signals of scatter factor/hepatocyte growth factor in epithelial cells. J Cell Biol. 1993; 121(1):145-54. PMC: 2119778. DOI: 10.1083/jcb.121.1.145. View

20.

Takaishi K, Sasaki T, Kato M, Yamochi W, Kuroda S, Nakamura T . Involvement of Rho p21 small GTP-binding protein and its regulator in the HGF-induced cell motility. Oncogene. 1994; 9(1):273-9. View