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
Communication between G protein-coupled receptors (GPCRs) and kinases is fundamental to human physiology. Most GPCRs are assumed to signal to kinases exclusively via second messenger cascades. In contrast, we recently found that during Hedgehog (Hh) signal transduction in development and disease, the atypical G protein-coupled receptor (GPCR) SMOOTHENED (SMO) signals intracellularly by binding the protein kinase A catalytic subunit (PKA-C) and physically blocking its enzymatic activity. How these SMO / PKA-C interactions are regulated, such that they only occur when SMO Is in an active state, remains unclear. Here we show that GPCR kinase 2 (GRK2) orchestrates SMO / PKA-C signaling during endogenous Hh pathway activation in its native subcellular location, the primary cilium. Upon SMO activation, GRK2 rapidly relocalizes from the ciliary base to the shaft, triggering SMO phosphorylation and PKA-C interaction. Reconstitution studies reveal that GRK2 phosphorylation enables active SMO to bind PKA-C directly. Lastly, the SMO-GRK2-PKA pathway underlies Hh signal transduction in a range of cellular and in vivo models. Thus, GRK2 phosphorylation of ciliary SMO, and the ensuing PKA-C binding and inactivation, are critical initiating events for the intracellular steps in Hh signaling. More broadly, our study suggests that direct GPCR-kinase communication mechanisms regulate many cellular signaling pathways. This work was supported by the National Institutes of Health grant 1R35GM133672.
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.
최근 본 자료 전체보기
