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 journalArticlepeer-review

14 Scopus citations

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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