{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPlatelet/endothelial cell adhesion molecule‐1 (PECAM‐1) is a quintessential vascular adhesion receptor that underpins the integrity and function of the endothelial barrier. It mediates homophilic interactions at cell–cell junctions that not only support steady‐state barrier properties and rapid repair after disruption but also enable endothelial migration and tube formation during angiogenesis. In addition, PECAM‐1 participates in mechanotransduction by responding to shear stress and mechanical stretch, thereby contributing to the organization of the cytoskeleton and the regulation of downstream signaling events critical for vessel morphogenesis and permeability."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in maintaining vascular homeostasis, PECAM‐1 is central to regulating leukocyte–endothelial interactions during inflammation. By engaging in homophilic ligation, it transmits “detachment” signals that prevent the inadvertent engulfment of viable leukocytes, while its redistribution and recycling at endothelial borders is crucial for guiding leukocytes during transendothelial migration. In this context PECAM‐1 not only facilitates diapedesis of neutrophils and other immune cells but also helps coordinate reverse migration processes of dendritic cells, thereby modulating immune surveillance and inflammatory responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOn the intracellular side, the cytoplasmic domain of PECAM‐1—featuring immunoreceptor tyrosine inhibitory motifs (ITIMs)—acts as a scaffold for specific signaling molecules, thereby modulating protein tyrosine phosphatases and kinases that control cell activation, integrin function, and apoptotic pathways. PECAM‐1 signaling regulates the suppression of pro‐apoptotic signals (for example, by counteracting Bax‐induced mitochondrial dysfunction) and is involved in mechanosensitive responses that activate partners such as Fyn and SHP2. 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