Protein tyrosine phosphatase interacting protein 51 during migration in HaCat cells

Abstract

The migration of cells in the human body is an important mechanism to support healing or to avoid inflammatory progresses. Therefore, the cells have to adapt and reorganise the cytoskeletal structure to actually create locomotion. The reorganisation and restructuring of the cytoskeleton filaments are regulated by the activation of specific actin binding proteins, of signal transductions pathways of membrane receptors and of kinases and phosphatases proteins. The protein tyrosine phosphates interacting protein (PTPIP51) regulates and facilitates with important signalling pathways, such as MAPK, calcium homeostasis, nuclear factor ĸB signalling and Akt signalling. PTPIP51 acts as a scaffold protein for signalling proteins, such as Her2 (human epidermal growth factor receptor 2), the EGFR (epidermal growth factor receptor), the IR (insulin receptor) and other scaffold proteins, e.g. 14.3-3-β. This review illuminates the PTPIP51 interactome in migrating HaCaT cells. The cells were grown to monolayers which were injured with a tip to induce the migration process. After the treatment with EGF (epidermal growth factor), insulin and LDC-3, the wound bed width was measured and the PTPIP51 interactome was detected by the Duolink proximity Assay and immunohistochemistry. PTPIP51 seem to stabilize and induce crucial cytoskeletal proteins such as the FAK (focal adhesion kinase), β-actin (also known as G-actin) and Rac-1 (Ras-related C3 botulinum toxin substrate 1). This study has shown that PTPIP51 is a very important interacting partner in migrating cells. When the cells were treated with the EGF, the PTPIP51/ Rac-1 interactions might induce the actin remodelling and also stabilize the lamellipodia itself through the integrins. Additionally, the PTPIP51/ G-actin interactome takes actual place of the F-actin filament growth on the leading edge. By treatment with insulin, the migration process gets induced through the PTPIP51/Rac-1 interactome, forming the F-actin filament through the PTPIP51/G-actin interactome on the leading edge, whereas the PTPIP51 stabilize the FAK on the integrin level plus prevents an overshoot of the MAPK pathway. The velocity of the migrating cells can be reduced by the dose and time dependency of LDC-3 treatment on the above-illustrated PTPIP51 interactome, plus prevents an overshoot of the MAPK activity. Future studies will show the importance of the PTPIP51 interactome with the interacting partners Rac-1, FAK and β-actin in carcinoma cell lines.