title: Protein-protein interaction between caveolin-1 and SHP-2 is dependent on the N-SH2 domain of SHP-2.
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.
authors: Department of Physiology, Tissue Injury Defense Research Center, Ewha Womans University School of Medicine, Seoul 158-710, Korea.
authors: Hyunju
authors: H
authors: Park
authors: Department of Science Education, Jeju National University, Jeju 690-756, Korea.
authors: Keun Jae
authors: KJ
authors: Ahn
authors: Department of Physiology, Tissue Injury Defense Research Center, Ewha Womans University School of Medicine, Seoul 158-710, Korea.
authors: Jihee
authors: J
authors: Lee Kang
authors: Department of Physiology, Tissue Injury Defense Research Center, Ewha Womans University School of Medicine, Seoul 158-710, Korea.
authors: Youn-Hee
authors: YH
authors: Choi
mesh_terms: D051242:Caveolin 1 / Q000378:metabolism*; D006801:Humans; D018384:Oxidative Stress; D010766:Phosphorylation; D011485:Protein Binding; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000737:chemistry / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D018909:src Homology Domains
chemical_list: D051242:Caveolin 1; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11