Hình ảnh cấu trúc của các tương tác kinase RAF

Biochemical Society Transactions - Tập 46 Số 6 - Trang 1393-1406 - 2018
Soheila Rezaei Adariani1, Marcel Buchholzer1, Mohammad Akbarzadeh1, Saeideh Nakhaei‐Rad1, Radovan Dvorský1, Mohammad Reza Ahmadian1
1Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany

Tóm tắt

RAF (fibrosarcoma gia tốc nhanh) Ser/Thr kinases (ARAF, BRAF, và CRAF) liên kết gia đình protein RAS (rat sarcoma) với con đường MAPK (kinase protein được kích hoạt bởi tác nhân gây tăng trưởng) và điều khiển sự tăng trưởng tế bào, phân hóa, phát triển, lão hóa và sinh ung thư. Hoạt động của chúng được điều chỉnh đặc biệt thông qua các tương tác protein-protein, các sửa đổi sau dịch mã, và sự thay đổi cấu hình trong các mẫu thời gian và không gian cụ thể qua nhiều điều tiết upstream, bao gồm các kinase, phosphatase, GTPases, và các protein khung và điều chỉnh. Việc khử phosphoryl hóa Ser-259 (theo số CRAF) và sự tách ra của 14-3-3 giải phóng các miền điều chỉnh của RAF, miền liên kết RAS và miền giàu cysteine, để tương tác với RAS-GTP và các lipid màng. Điều này dẫn đến việc phosphoryl hóa RAF tại Ser-621 và sự tái kết hợp 14-3-3, tiếp theo là sự dimer hóa của nó và cuối cùng là sự liên kết và phosphoryl hóa cơ chất. Bài tổng quan này tập trung vào việc hiểu cấu trúc cách mà các đối tác liên kết khác nhau kích hoạt một chuỗi sự kiện phân tử dẫn đến việc kích hoạt kinase RAF.

Từ khóa


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