Below the Surface: IGF-1R Therapeutic Targeting and Its Endocytic Journey

Cells

卷:8

GeorgeA. Calin¹  Eric Trocmé²  Ada Girnita²  Sylvya Pasca²  Leonard Girnita²  Sonia Cismas²  Caitrin Crudden²  Dawei Song² 

[1] Department of Experimental Therapeutics, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA;

[2] Department of Oncology-Pathology, Cellular and Molecular Tumor Pathology, Karolinska Institute, and Karolinska University Hospital, 17164 Stockholm, Sweden;

关键词: insulin-like growth factor type 1 receptor;    insulin receptor;    rtk;    gpcr;    internalization;    endocytosis;    endosome;    biased signaling;    ubiquitination;    β-arrestin;   

DOI  :  10.3390/cells8101223

来源: DOAJ

【 摘 要 】

Ligand-activated plasma membrane receptors follow pathways of endocytosis through the endosomal sorting apparatus. Receptors cluster in clathrin-coated pits that bud inwards and enter the cell as clathrin-coated vesicles. These vesicles travel through the acidic endosome whereby receptors and ligands are sorted to be either recycled or degraded. The traditional paradigm postulated that the endocytosis role lay in signal termination through the removal of the receptor from the cell surface. It is now becoming clear that the internalization process governs more than receptor signal cessation and instead reigns over the entire spatial and temporal wiring of receptor signaling. Governing the localization, the post-translational modifications, and the scaffolding of receptors and downstream signal components established the endosomal platform as the master regulator of receptor function. Confinement of components within or between distinct organelles means that the endosome instructs the cell on how to interpret and translate the signal emanating from any given receptor complex into biological effects. This review explores this emerging paradigm with respect to the cancer-relevant insulin-like growth factor type 1 receptor (IGF-1R) and discusses how this perspective could inform future targeting strategies.

【 授权许可】

Unknown