A novel role for H-Ras in the regulation of very late antigen-4 integrin and VCAM-1 via c-Myc-dependent and -independent mechanisms

Zhao-Jun Liu, Yoshiya Tanaka, Hiroko Fujimoto, Shinichiro Mine, Akio Morinobu, Hideo Yagita, Ko Okumura, Isao Oishi, Jun Udagawa, Hirohei Yamamura, Yasuhiro Minami

Research output: Contribution to journalArticle

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Abstract

Despite extensive studies on the crucial functions of Ras and c-Myc in cellular proliferation and transformation, their roles in regulating cell adhesion are not yet fully understood. Involvement of Ras in modulating integrin activity by inside-out signaling has been recently reported. However, in contrast to R-Ras, H-Ras was found to exhibit a suppressive effect. Here we show that ectopic expression of a constitutively active H- Ras(v12), but not c-Myc alone, in a hemopoietic cell line induces activation of very late Ag-4 (VLA-4, α4β1) integrin without changing its surface expression. Intriguingly, coexpression of H-Ras(v12) and c-Myc in these cells results in not only the activation of VLA-4, but also the induction of expression of VCAM-1, the counterreceptor for VLA-4, thereby mediating a marked homotypic cell aggregation. In addition, H-Ras(v12)-induced VLA-4 activation appears to be partly down-regulated by coexpression with c-Myc. Our results represent an unprecedented example demonstrating a novel role for H-Ras(v12) in the regulation of cell adhesion via c-Myc-independent and - dependent mechanisms.

Original languageEnglish
Pages (from-to)4901-4908
Number of pages8
JournalJournal of Immunology
Volume163
Issue number9
StatePublished - Nov 6 1999
Externally publishedYes

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Integrin alpha4beta1
Vascular Cell Adhesion Molecule-1
Integrins
Cell Adhesion
Cell Aggregation
Cell Proliferation
Cell Line

ASJC Scopus subject areas

  • Immunology

Cite this

Liu, Z-J., Tanaka, Y., Fujimoto, H., Mine, S., Morinobu, A., Yagita, H., ... Minami, Y. (1999). A novel role for H-Ras in the regulation of very late antigen-4 integrin and VCAM-1 via c-Myc-dependent and -independent mechanisms. Journal of Immunology, 163(9), 4901-4908.

A novel role for H-Ras in the regulation of very late antigen-4 integrin and VCAM-1 via c-Myc-dependent and -independent mechanisms. / Liu, Zhao-Jun; Tanaka, Yoshiya; Fujimoto, Hiroko; Mine, Shinichiro; Morinobu, Akio; Yagita, Hideo; Okumura, Ko; Oishi, Isao; Udagawa, Jun; Yamamura, Hirohei; Minami, Yasuhiro.

In: Journal of Immunology, Vol. 163, No. 9, 06.11.1999, p. 4901-4908.

Research output: Contribution to journalArticle

Liu, Z-J, Tanaka, Y, Fujimoto, H, Mine, S, Morinobu, A, Yagita, H, Okumura, K, Oishi, I, Udagawa, J, Yamamura, H & Minami, Y 1999, 'A novel role for H-Ras in the regulation of very late antigen-4 integrin and VCAM-1 via c-Myc-dependent and -independent mechanisms', Journal of Immunology, vol. 163, no. 9, pp. 4901-4908.
Liu, Zhao-Jun ; Tanaka, Yoshiya ; Fujimoto, Hiroko ; Mine, Shinichiro ; Morinobu, Akio ; Yagita, Hideo ; Okumura, Ko ; Oishi, Isao ; Udagawa, Jun ; Yamamura, Hirohei ; Minami, Yasuhiro. / A novel role for H-Ras in the regulation of very late antigen-4 integrin and VCAM-1 via c-Myc-dependent and -independent mechanisms. In: Journal of Immunology. 1999 ; Vol. 163, No. 9. pp. 4901-4908.
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