β2-Chimaerin binds to EphA receptors and regulates cell migration

Takeuchi, Shingo; Yamaki, Nao; Iwasato, Takuji; Negishi, Manabu; Katoh, Hironori

doi:10.1016/j.febslet.2009.03.032

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Volume 583, Issue 8 , Pages 1237-1242, 17 April 2009

β2-Chimaerin binds to EphA receptors and regulates cell migration

Edited by Beat Imhof

Shingo Takeuchi
- Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
Nao Yamaki
- Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
Takuji Iwasato
- Department of Developmental Genetics, National Institute of Genetics, 1111 Yata Mishima, Shizuoka 411-8540, Japan
Manabu Negishi
- Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
Hironori Katoh
- Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
- Corresponding author. Fax: +81 75 753 7688.

Received 19 January 2009; received in revised form 13 March 2009; accepted 16 March 2009. published online 23 March 2009.

Abstract

Ephrins and Eph receptors have key roles in regulation of cell migration during development. We found that the RacGAP β2-chimaerin (chimerin) bound to EphA2 and EphA4 and inactivated Rac1 in response to ephrinA1 stimulation. EphA4 bound to β2-chimaerin through its kinase domain and promoted binding of Rac1 to β2-chimaerin. In addition, knockdown of endogenous β2-chimaerin blocked ephrinA1-induced suppression of cell migration. These results suggest that β2-chimaerin is activated by EphA receptors and mediates the EphA receptor-dependent regulation of cell migration.

Structured summary

MINT-7013428: EphA1 (uniprotkb:Q60750) physically interacts (MI:0218) with Chimaerin beta 2 (uniprotkb:Q80XD1-2) and EphA4 (uniprotkb:O08542) by anti tag coimmunoprecipitation (MI:0007)

MINT-7013515: Chimaerin beta 2 (uniprotkb:Q80XD1-2) physically interacts (MI:0218) with Rac1 (uniprotkb:P63001) by anti tag coimmunoprecipitation (MI:0007)

MINT-7013410: EphA1 (uniprotkb:Q60750) physically interacts (MI:0218) with Chimaerin beta 1 (uniprotkb:Q80XD1-1) and EphA4 (uniprotkb:O08542) by anti tag coimmunoprecipitation (MI:0007)

MINT-7013503: Chimaerin beta 1 (uniprotkb:Q80XD1-1) physically interacts (MI:0218) with EphA4 (uniprotkb:O08542) by anti tag coimmunoprecipitation (MI:0007)

MINT-7013472: Chimaerin beta 2 (uniprotkb:Q80XD1-2) physically interacts (MI:0218) with EphA2 (uniprotkb:O43921) by anti tag coimmunoprecipitation (MI:0007)

MINT-7013450: EphA1 (uniprotkb:Q60750) physically interacts (MI:0218) with EphA2 (uniprotkb:O43921) and Chimaerin beta 2 (uniprotkb:P52757-1) by anti tag coimmunoprecipitation (MI:0007)

MINT-7013491: Chimaerin beta 2 (uniprotkb:Q80XD1-2) physically interacts (MI:0218) with EphA4 (uniprotkb:O08542) by anti tag coimmunoprecipitation (MI:0007)

Abbreviations: GAP, GTPase-activating protein, DAG, diacylglycerol, SH2, Src-homology 2, RT, reverse transcriptase, EYFP, enhanced yellow fluorescent protein, shRNA, short hairpin RNA, GAPDH, glyceraldehyde-3-phosphate dehydrogenase