Lipid-driven Src self-association modulates its transformation capacity.

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Tác giả: Yvan Boublik, Alejandro Fernández, Elise Fourgous, Marina I Giannotti, Anabel-Lise Le Roux, Irrem-Laareb Mohammad, Miquel Pons, Serge Roche, Audrey Sirvent, Marta Taulés

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: United States : Life science alliance , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 718105

Src tyrosine kinase regulates cell growth and adhesion through membrane signaling, and its deregulation is associated with cancer. Although active Src is anchored to the plasma membrane, the role of membrane lipids in its regulation remains unclear. Here, we report that Src self-associates via a lysine cluster in its SH4 region, a process mediated by lipids in human cells and in vitro. Mutation of the lysine cluster to arginine alters Src self-association and modulates its transforming function in human cells. Lipid-anchored micron-sized condensates of full-length Src form in supported homogeneous lipid bilayers (i.e., independently of lipid phase separation). Condensates also arise from the purified Src N-terminal regulatory element, which includes the myristoylated SH4 domain, the intrinsically disordered Unique domain, and the globular SH3 domain. However, the isolated SH4 domain alone forms small protein-lipid clusters rather than micron-sized condensates. Our findings reveal lipid-mediated kinase self-association as an additional regulatory mechanism for Src. This mechanism may also apply to other membrane-associated signaling proteins containing similar lysine clusters in their unstructured regions.
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