TY - JOUR
T1 - Redistribution of ERK/MAP kinase to uropod-like structures in interleukin-3-induced cell shape changes
AU - Mera, Akihiko
AU - Suga, Moritaka
AU - Nakayama, Yuji
AU - Ando, Masayuki
AU - Suda, Toshio
AU - Yamaguchi, Naoto
N1 - Funding Information:
We are grateful to Dr Michio Hagiya and Toyohiro Takehara (Toyobo Co. Ltd) and Dr Tetsuo Sudo (Toray Industries, Inc) for generously providing MSP and IL-3. We also thank Dr Naoto Oku (University of Shizuoka, Shizuoka) for his encouragement throughout this study. This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan.
PY - 2002/11/1
Y1 - 2002/11/1
N2 - Interleukin-3 (IL-3) is one of the cytokines of significance for the regulation of hematopoiesis and inflammation. Recently, we established IL-3-dependent Ba/F3 pro-B cells ectopically expressing RON tyrosine kinase, a receptor for macrophage-stimulating protein (MSP), and showed that MSP stimulation specifically promoted cell morphological changes through tyrosine phosphorylation of the IL-3 common β-chain receptor subunit (βc) by activated RON kinase without activation of JAK2 tyrosine kinase. Here we investigate the IL-3 signaling pathway leading to morphological changes through tyrosine phosphorylation of βc. Treatment of RON-expressing cells with PD98059 or U0126, inhibitors of mitogen-activated protein kinase kinase activity, blocked both IL-3- and MSP-induced morphological changes. Upon stimulation with IL-3 or MSP, extracellular-regulated kinase (ERK) and F-actin were redistributed in uropod-like structures. ERK and F-actin were colocalized within uropod-like structures, and a majority of F-actin were localized around the peripheries of accumulated ERK. Tyrosine phosphorylation of ERK was detected after stimulation with IL-3 or MSP, whereas treatment with U0126 specifically inhibited IL-3- or MSP-induced ERK phosphorylation but not tyrosine phosphorylation of βc. These results suggest that the activation and localization of ERK to uropod-like structures play a role in IL-3-induced morphological changes.
AB - Interleukin-3 (IL-3) is one of the cytokines of significance for the regulation of hematopoiesis and inflammation. Recently, we established IL-3-dependent Ba/F3 pro-B cells ectopically expressing RON tyrosine kinase, a receptor for macrophage-stimulating protein (MSP), and showed that MSP stimulation specifically promoted cell morphological changes through tyrosine phosphorylation of the IL-3 common β-chain receptor subunit (βc) by activated RON kinase without activation of JAK2 tyrosine kinase. Here we investigate the IL-3 signaling pathway leading to morphological changes through tyrosine phosphorylation of βc. Treatment of RON-expressing cells with PD98059 or U0126, inhibitors of mitogen-activated protein kinase kinase activity, blocked both IL-3- and MSP-induced morphological changes. Upon stimulation with IL-3 or MSP, extracellular-regulated kinase (ERK) and F-actin were redistributed in uropod-like structures. ERK and F-actin were colocalized within uropod-like structures, and a majority of F-actin were localized around the peripheries of accumulated ERK. Tyrosine phosphorylation of ERK was detected after stimulation with IL-3 or MSP, whereas treatment with U0126 specifically inhibited IL-3- or MSP-induced ERK phosphorylation but not tyrosine phosphorylation of βc. These results suggest that the activation and localization of ERK to uropod-like structures play a role in IL-3-induced morphological changes.
KW - ERK
KW - IL-3
KW - MSP
KW - Morphological change
KW - RON
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U2 - 10.1016/S0165-2478(02)00132-3
DO - 10.1016/S0165-2478(02)00132-3
M3 - Article
C2 - 12270548
AN - SCOPUS:0036830591
VL - 84
SP - 117
EP - 124
JO - Immunology Letters
JF - Immunology Letters
SN - 0165-2478
IS - 2
ER -