인문학
사회과학
자연과학
공학
의약학
농수해양학
예술체육학
복합학
DBpia AI
AI 에이전트
AI 아이디어
AI 리더
AI 뷰어
Citeasy
크롬 서지관리 다운로드
지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
초록·키워드
Janus Kinase-1 (JAK1) plays key roles during neurodevelopment and following neuronal injury, while activatory JAK1 mutations are linked to leukemia. In mice, Jak1 genetic deletion results in perinatal lethality, suggesting non-redundant roles and/or regulation of JAK1 for which other JAKs cannot compensate. Proteomic studies reveal that JAK1 is more likely palmitoylated compared to other JAKs, implicating palmitoylation as a possible JAK1-specific regulatory mechanism. However, the importance of palmitoylation for JAK1 signaling has not been addressed. Here, we report that JAK1 is palmitoylated in transfected HEK293T cells and endogenously in cultured Dorsal Root Ganglion (DRG) neurons. We further use comprehensive screening in transfected non-neuronal cells and shRNA-mediated knockdown in DRG neurons to identify the related enzymes ZDHHC3 and ZDHHC7 as dominant protein acyltransferases (PATs) for JAK1. Surprisingly, we found palmitoylation minimally affects JAK1 localization in neurons, but is critical for JAK1's kinase activity in cells and even in vitro. We propose this requirement is likely because palmitoylation facilitates transphosphorylation of key sites in JAK1's activation loop, a possibility consistent with structural models of JAK1. Importantly, we demonstrate a leukemia-associated JAK1 mutation overrides the palmitoylation-dependence of JAK1 activity, potentially explaining why this mutation is oncogenic. Finally, we show that JAK1 palmitoylation is important for neuropoietic cytokine-dependent signaling and neuronal survival and that combined Zdhhc3/7 loss phenocopies loss of palmitoyl-JAK1. These findings provide new insights into the control of JAK signaling in both physiological and pathological contexts.
인공지능 문자 인식 모델을 통해 추출된 텍스트로, 일부 오타나 오류가 포함될 수 있으나 지속적으로 개선 중입니다.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.
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