H-Ras signals to cytoskeletal machinery in induction of integrin-mediated adhesion of T cells

Y Tanaka, Y Minami, S Mine, H Hirano, C D Hu, H Fujimoto, K Fujii, K Saito, J Tsukada, Y van Kooyk, C G Figdor, T Kataoka, S Eto

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The adhesive function of integrins is regulated through cytoplasmic signaling. The present study was performed to investigate the relevance of cytoplasmic signaling and cytoskeletal assembly to integrin-mediated adhesion induced by chemokines. Adhesion of T cells induced by chemokines macrophage inflammatory protein (MIP)-1alpha and MIP-1beta was inhibited by pertussis toxin, wortmannin, and cytochalasin B, suggesting that both G protein-sensitive phosphatidylinositol (PI) 3-kinase activation and cytoskeletal assemblies are involved. The chemokine-induced T cell adhesion could be mimicked by expression of small G proteins, fully activated H-RasV12, or H-RasV12Y40C mutant, which selectively binds to PI 3-kinase, in T cells, inducing activated form of LFA-1alpha and LFA-1-dependent adhesion to ICAM-1. H-Ras expression also induced F-actin polymerization which colocalized with profilin in T cells. Adult T cell leukemia (ATL) cells spontaneously adhered to ICAM-1, which depended on endogenous MIP-1alpha and MIP-1beta through activation of G protein-sensitive PI 3-kinase. H-Ras signal pathway, leading to PI 3-kinase activation, also induced active configuration of LFA-1 and LFA-1-mediated adhesion of ATL cells, whereas expression of a dominant-negative H-Ras mutant failed to do. Profilin-dependent spontaneous polymerization of F-actin in ATL cells was reduced by PI 3-kinase inhibitors. In this paper we propose that H-Ras-mediated activation of PI 3-kinase can be involved in induction of LFA-1-dependent adhesion of T cells, which is relevant to chemokine-mediated signaling, and that profilin may form an important link between chemokine- and/or H-Ras-mediated signals and F-actin polymerization, which results in triggering of LFA-1 on T cells or leukemic T cells.

Original languageEnglish
Pages (from-to)6209-16
Number of pages8
JournalJournal of Immunology
Volume163
Issue number11
Publication statusPublished - 1 Dec 1999

Cite this

Tanaka, Y., Minami, Y., Mine, S., Hirano, H., Hu, C. D., Fujimoto, H., ... Eto, S. (1999). H-Ras signals to cytoskeletal machinery in induction of integrin-mediated adhesion of T cells. Journal of Immunology, 163(11), 6209-16.
Tanaka, Y ; Minami, Y ; Mine, S ; Hirano, H ; Hu, C D ; Fujimoto, H ; Fujii, K ; Saito, K ; Tsukada, J ; van Kooyk, Y ; Figdor, C G ; Kataoka, T ; Eto, S. / H-Ras signals to cytoskeletal machinery in induction of integrin-mediated adhesion of T cells. In: Journal of Immunology. 1999 ; Vol. 163, No. 11. pp. 6209-16.
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abstract = "The adhesive function of integrins is regulated through cytoplasmic signaling. The present study was performed to investigate the relevance of cytoplasmic signaling and cytoskeletal assembly to integrin-mediated adhesion induced by chemokines. Adhesion of T cells induced by chemokines macrophage inflammatory protein (MIP)-1alpha and MIP-1beta was inhibited by pertussis toxin, wortmannin, and cytochalasin B, suggesting that both G protein-sensitive phosphatidylinositol (PI) 3-kinase activation and cytoskeletal assemblies are involved. The chemokine-induced T cell adhesion could be mimicked by expression of small G proteins, fully activated H-RasV12, or H-RasV12Y40C mutant, which selectively binds to PI 3-kinase, in T cells, inducing activated form of LFA-1alpha and LFA-1-dependent adhesion to ICAM-1. H-Ras expression also induced F-actin polymerization which colocalized with profilin in T cells. Adult T cell leukemia (ATL) cells spontaneously adhered to ICAM-1, which depended on endogenous MIP-1alpha and MIP-1beta through activation of G protein-sensitive PI 3-kinase. H-Ras signal pathway, leading to PI 3-kinase activation, also induced active configuration of LFA-1 and LFA-1-mediated adhesion of ATL cells, whereas expression of a dominant-negative H-Ras mutant failed to do. Profilin-dependent spontaneous polymerization of F-actin in ATL cells was reduced by PI 3-kinase inhibitors. In this paper we propose that H-Ras-mediated activation of PI 3-kinase can be involved in induction of LFA-1-dependent adhesion of T cells, which is relevant to chemokine-mediated signaling, and that profilin may form an important link between chemokine- and/or H-Ras-mediated signals and F-actin polymerization, which results in triggering of LFA-1 on T cells or leukemic T cells.",
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author = "Y Tanaka and Y Minami and S Mine and H Hirano and Hu, {C D} and H Fujimoto and K Fujii and K Saito and J Tsukada and {van Kooyk}, Y and Figdor, {C G} and T Kataoka and S Eto",
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Tanaka, Y, Minami, Y, Mine, S, Hirano, H, Hu, CD, Fujimoto, H, Fujii, K, Saito, K, Tsukada, J, van Kooyk, Y, Figdor, CG, Kataoka, T & Eto, S 1999, 'H-Ras signals to cytoskeletal machinery in induction of integrin-mediated adhesion of T cells' Journal of Immunology, vol. 163, no. 11, pp. 6209-16.

H-Ras signals to cytoskeletal machinery in induction of integrin-mediated adhesion of T cells. / Tanaka, Y; Minami, Y; Mine, S; Hirano, H; Hu, C D; Fujimoto, H; Fujii, K; Saito, K; Tsukada, J; van Kooyk, Y; Figdor, C G; Kataoka, T; Eto, S.

In: Journal of Immunology, Vol. 163, No. 11, 01.12.1999, p. 6209-16.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - H-Ras signals to cytoskeletal machinery in induction of integrin-mediated adhesion of T cells

AU - Tanaka, Y

AU - Minami, Y

AU - Mine, S

AU - Hirano, H

AU - Hu, C D

AU - Fujimoto, H

AU - Fujii, K

AU - Saito, K

AU - Tsukada, J

AU - van Kooyk, Y

AU - Figdor, C G

AU - Kataoka, T

AU - Eto, S

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N2 - The adhesive function of integrins is regulated through cytoplasmic signaling. The present study was performed to investigate the relevance of cytoplasmic signaling and cytoskeletal assembly to integrin-mediated adhesion induced by chemokines. Adhesion of T cells induced by chemokines macrophage inflammatory protein (MIP)-1alpha and MIP-1beta was inhibited by pertussis toxin, wortmannin, and cytochalasin B, suggesting that both G protein-sensitive phosphatidylinositol (PI) 3-kinase activation and cytoskeletal assemblies are involved. The chemokine-induced T cell adhesion could be mimicked by expression of small G proteins, fully activated H-RasV12, or H-RasV12Y40C mutant, which selectively binds to PI 3-kinase, in T cells, inducing activated form of LFA-1alpha and LFA-1-dependent adhesion to ICAM-1. H-Ras expression also induced F-actin polymerization which colocalized with profilin in T cells. Adult T cell leukemia (ATL) cells spontaneously adhered to ICAM-1, which depended on endogenous MIP-1alpha and MIP-1beta through activation of G protein-sensitive PI 3-kinase. H-Ras signal pathway, leading to PI 3-kinase activation, also induced active configuration of LFA-1 and LFA-1-mediated adhesion of ATL cells, whereas expression of a dominant-negative H-Ras mutant failed to do. Profilin-dependent spontaneous polymerization of F-actin in ATL cells was reduced by PI 3-kinase inhibitors. In this paper we propose that H-Ras-mediated activation of PI 3-kinase can be involved in induction of LFA-1-dependent adhesion of T cells, which is relevant to chemokine-mediated signaling, and that profilin may form an important link between chemokine- and/or H-Ras-mediated signals and F-actin polymerization, which results in triggering of LFA-1 on T cells or leukemic T cells.

AB - The adhesive function of integrins is regulated through cytoplasmic signaling. The present study was performed to investigate the relevance of cytoplasmic signaling and cytoskeletal assembly to integrin-mediated adhesion induced by chemokines. Adhesion of T cells induced by chemokines macrophage inflammatory protein (MIP)-1alpha and MIP-1beta was inhibited by pertussis toxin, wortmannin, and cytochalasin B, suggesting that both G protein-sensitive phosphatidylinositol (PI) 3-kinase activation and cytoskeletal assemblies are involved. The chemokine-induced T cell adhesion could be mimicked by expression of small G proteins, fully activated H-RasV12, or H-RasV12Y40C mutant, which selectively binds to PI 3-kinase, in T cells, inducing activated form of LFA-1alpha and LFA-1-dependent adhesion to ICAM-1. H-Ras expression also induced F-actin polymerization which colocalized with profilin in T cells. Adult T cell leukemia (ATL) cells spontaneously adhered to ICAM-1, which depended on endogenous MIP-1alpha and MIP-1beta through activation of G protein-sensitive PI 3-kinase. H-Ras signal pathway, leading to PI 3-kinase activation, also induced active configuration of LFA-1 and LFA-1-mediated adhesion of ATL cells, whereas expression of a dominant-negative H-Ras mutant failed to do. Profilin-dependent spontaneous polymerization of F-actin in ATL cells was reduced by PI 3-kinase inhibitors. In this paper we propose that H-Ras-mediated activation of PI 3-kinase can be involved in induction of LFA-1-dependent adhesion of T cells, which is relevant to chemokine-mediated signaling, and that profilin may form an important link between chemokine- and/or H-Ras-mediated signals and F-actin polymerization, which results in triggering of LFA-1 on T cells or leukemic T cells.

KW - Actins/metabolism

KW - Adult

KW - Androstadienes/pharmacology

KW - Arthritis, Rheumatoid

KW - Cell Adhesion/physiology

KW - Chemokine CCL3

KW - Chemokine CCL4

KW - Contractile Proteins

KW - Cytochalasin B/pharmacology

KW - Cytoskeleton/physiology

KW - Endothelium, Vascular/cytology

KW - GTP-Binding Proteins/metabolism

KW - Genes, ras/physiology

KW - Humans

KW - Integrins/metabolism

KW - Intercellular Adhesion Molecule-1/metabolism

KW - Leukemia, T-Cell

KW - Lymphocyte Function-Associated Antigen-1/metabolism

KW - Macrophage Inflammatory Proteins/metabolism

KW - Microfilament Proteins/metabolism

KW - Phosphatidylinositol 3-Kinases/metabolism

KW - Profilins

KW - Signal Transduction

KW - T-Lymphocytes/physiology

M3 - Article

VL - 163

SP - 6209

EP - 6216

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 11

ER -

Tanaka Y, Minami Y, Mine S, Hirano H, Hu CD, Fujimoto H et al. H-Ras signals to cytoskeletal machinery in induction of integrin-mediated adhesion of T cells. Journal of Immunology. 1999 Dec 1;163(11):6209-16.