Src and SHP2 coordinately regulate the dynamics and organization of vimentin filaments during cell migration

Cheng Yi Yang, Po Wei Chang, Wen Hsin Hsu, Hsuan Chia Chang, Chien Lin Chen, Chien Chen Lai, Wen-Tai Chiu, Hong Chen Chen

Research output: Contribution to journalArticle

Abstract

Vimentin intermediate filaments (VIFs), expressed in most mesenchymal and cancer cells, undergo dramatic reorganization during cell migration; however, the mechanism remains obscure. This study demonstrates that upon growth-factor stimulation, Src directly phosphorylates vimentin at Tyr117, leading to VIF disassembly into squiggles and particles at the cell edge during lamellipodia formation. The protein tyrosine phosphatase SHP2 counteracted the Src effects on VIF tyrosine phosphorylation and organization. VIFs formed by vimentin Y117D mutant were more soluble and dynamic than those formed by the wild-type and Y117F mutant. Increased expression of vimentin promoted growth-factor induced lamellipodia formation and cell migration, whereas the mutants suppressed both. The vimentin-induced increase in lamellipodia formation correlated with the activation of Rac and Vav2, with the latter associated with VIFs and recruited to the plasma membrane upon growth-factor stimulation. These results reveal a novel mechanism for regulating VIF dynamics through Src and SHP2 and demonstrate that proper VIF dynamics are important for Rac activation and cell migration.

Original languageEnglish
Pages (from-to)4075-4094
Number of pages20
JournalOncogene
Volume38
Issue number21
DOIs
Publication statusPublished - 2019 May 23

Fingerprint

Vimentin
Cell Movement
Intermediate Filaments
Pseudopodia
Intercellular Signaling Peptides and Proteins
Protein Tyrosine Phosphatases
Tyrosine
Phosphorylation
Cell Membrane

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Yang, C. Y., Chang, P. W., Hsu, W. H., Chang, H. C., Chen, C. L., Lai, C. C., ... Chen, H. C. (2019). Src and SHP2 coordinately regulate the dynamics and organization of vimentin filaments during cell migration. Oncogene, 38(21), 4075-4094. https://doi.org/10.1038/s41388-019-0705-x
Yang, Cheng Yi ; Chang, Po Wei ; Hsu, Wen Hsin ; Chang, Hsuan Chia ; Chen, Chien Lin ; Lai, Chien Chen ; Chiu, Wen-Tai ; Chen, Hong Chen. / Src and SHP2 coordinately regulate the dynamics and organization of vimentin filaments during cell migration. In: Oncogene. 2019 ; Vol. 38, No. 21. pp. 4075-4094.
@article{c77f8155ed864860811e2b71ad16ec26,
title = "Src and SHP2 coordinately regulate the dynamics and organization of vimentin filaments during cell migration",
abstract = "Vimentin intermediate filaments (VIFs), expressed in most mesenchymal and cancer cells, undergo dramatic reorganization during cell migration; however, the mechanism remains obscure. This study demonstrates that upon growth-factor stimulation, Src directly phosphorylates vimentin at Tyr117, leading to VIF disassembly into squiggles and particles at the cell edge during lamellipodia formation. The protein tyrosine phosphatase SHP2 counteracted the Src effects on VIF tyrosine phosphorylation and organization. VIFs formed by vimentin Y117D mutant were more soluble and dynamic than those formed by the wild-type and Y117F mutant. Increased expression of vimentin promoted growth-factor induced lamellipodia formation and cell migration, whereas the mutants suppressed both. The vimentin-induced increase in lamellipodia formation correlated with the activation of Rac and Vav2, with the latter associated with VIFs and recruited to the plasma membrane upon growth-factor stimulation. These results reveal a novel mechanism for regulating VIF dynamics through Src and SHP2 and demonstrate that proper VIF dynamics are important for Rac activation and cell migration.",
author = "Yang, {Cheng Yi} and Chang, {Po Wei} and Hsu, {Wen Hsin} and Chang, {Hsuan Chia} and Chen, {Chien Lin} and Lai, {Chien Chen} and Wen-Tai Chiu and Chen, {Hong Chen}",
year = "2019",
month = "5",
day = "23",
doi = "10.1038/s41388-019-0705-x",
language = "English",
volume = "38",
pages = "4075--4094",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "21",

}

Yang, CY, Chang, PW, Hsu, WH, Chang, HC, Chen, CL, Lai, CC, Chiu, W-T & Chen, HC 2019, 'Src and SHP2 coordinately regulate the dynamics and organization of vimentin filaments during cell migration', Oncogene, vol. 38, no. 21, pp. 4075-4094. https://doi.org/10.1038/s41388-019-0705-x

Src and SHP2 coordinately regulate the dynamics and organization of vimentin filaments during cell migration. / Yang, Cheng Yi; Chang, Po Wei; Hsu, Wen Hsin; Chang, Hsuan Chia; Chen, Chien Lin; Lai, Chien Chen; Chiu, Wen-Tai; Chen, Hong Chen.

In: Oncogene, Vol. 38, No. 21, 23.05.2019, p. 4075-4094.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Src and SHP2 coordinately regulate the dynamics and organization of vimentin filaments during cell migration

AU - Yang, Cheng Yi

AU - Chang, Po Wei

AU - Hsu, Wen Hsin

AU - Chang, Hsuan Chia

AU - Chen, Chien Lin

AU - Lai, Chien Chen

AU - Chiu, Wen-Tai

AU - Chen, Hong Chen

PY - 2019/5/23

Y1 - 2019/5/23

N2 - Vimentin intermediate filaments (VIFs), expressed in most mesenchymal and cancer cells, undergo dramatic reorganization during cell migration; however, the mechanism remains obscure. This study demonstrates that upon growth-factor stimulation, Src directly phosphorylates vimentin at Tyr117, leading to VIF disassembly into squiggles and particles at the cell edge during lamellipodia formation. The protein tyrosine phosphatase SHP2 counteracted the Src effects on VIF tyrosine phosphorylation and organization. VIFs formed by vimentin Y117D mutant were more soluble and dynamic than those formed by the wild-type and Y117F mutant. Increased expression of vimentin promoted growth-factor induced lamellipodia formation and cell migration, whereas the mutants suppressed both. The vimentin-induced increase in lamellipodia formation correlated with the activation of Rac and Vav2, with the latter associated with VIFs and recruited to the plasma membrane upon growth-factor stimulation. These results reveal a novel mechanism for regulating VIF dynamics through Src and SHP2 and demonstrate that proper VIF dynamics are important for Rac activation and cell migration.

AB - Vimentin intermediate filaments (VIFs), expressed in most mesenchymal and cancer cells, undergo dramatic reorganization during cell migration; however, the mechanism remains obscure. This study demonstrates that upon growth-factor stimulation, Src directly phosphorylates vimentin at Tyr117, leading to VIF disassembly into squiggles and particles at the cell edge during lamellipodia formation. The protein tyrosine phosphatase SHP2 counteracted the Src effects on VIF tyrosine phosphorylation and organization. VIFs formed by vimentin Y117D mutant were more soluble and dynamic than those formed by the wild-type and Y117F mutant. Increased expression of vimentin promoted growth-factor induced lamellipodia formation and cell migration, whereas the mutants suppressed both. The vimentin-induced increase in lamellipodia formation correlated with the activation of Rac and Vav2, with the latter associated with VIFs and recruited to the plasma membrane upon growth-factor stimulation. These results reveal a novel mechanism for regulating VIF dynamics through Src and SHP2 and demonstrate that proper VIF dynamics are important for Rac activation and cell migration.

UR - http://www.scopus.com/inward/record.url?scp=85060793813&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85060793813&partnerID=8YFLogxK

U2 - 10.1038/s41388-019-0705-x

DO - 10.1038/s41388-019-0705-x

M3 - Article

C2 - 30696956

AN - SCOPUS:85060793813

VL - 38

SP - 4075

EP - 4094

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 21

ER -