Protein-protein interaction between caveolin-1 and SHP-2 is dependent on the N-SH2 domain of SHP-2 |
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Authors: | Hyunju Park Keun Jae Ahn Jihee Lee Kang Youn-Hee Choi |
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Affiliation: | 1.Department of Physiology, Tissue Injury Defense Research Center, Ewha Womans University School of Medicine, Seoul 158-710, Korea;2.Department of Science Education, Jeju National University, Jeju 690-756, Korea |
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Abstract: | Src homology 2-containing protein tyrosine phosphatase 2 (SHP-2) is known to protect neurons from neurodegeneration during ischemia/reperfusion injury. We recently reported that ROS-mediated oxidative stress promotes phosphorylation of endogenous SHP-2 in astrocytes and complex formation between caveolin-1 and SHP-2 in response to oxidative stress. To examine the region of SHP-2 participating in complex formation with caveolin-1, we generated three deletion mutant constructs and six point mutation constructs of SHP-2. Compared with wild-type SHP-2, binding of the N-SH2 domain deletion mutant of SHP-2 to p-caveolin-1 was reduced greatly, using flow cytometric competitive binding assays and surface plasmon resonance (SPR). Moreover, deletion of the N-SH2 domain of SHP-2 affected H2O2-mediated ERK phosphorylation and Src phosphorylation at Tyr 419 in primary astrocytes, suggesting that N-SH2 domain of SHP-2 is responsible for the binding of caveolin-1 and contributes to the regulation of Src phosphorylation and activation following ROS-induced oxidative stress in brain astrocytes. [BMB Reports 2015; 48(3): 184-189] |
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Keywords: | Astrocytes Caveolin-1 Reactive oxygen species SHP-2 Src |
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