Silverstein Roy L, Febbraio Maria
Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44195, USA.
Sci Signal. 2009 May 26;2(72):re3. doi: 10.1126/scisignal.272re3.
CD36 is a membrane glycoprotein present on platelets, mononuclear phagocytes, adipocytes, hepatocytes, myocytes, and some epithelia. On microvascular endothelial cells, CD36 is a receptor for thrombospondin-1 and related proteins and functions as a negative regulator of angiogenesis. On phagocytes, through its functions as a scavenger receptor recognizing specific oxidized phospholipids and lipoproteins, CD36 participates in internalization of apoptotic cells, certain bacterial and fungal pathogens, and modified low-density lipoproteins, thus contributing to inflammatory responses and atherothrombotic diseases. CD36 also binds long-chain fatty acids and facilitates their transport into cells, thus participating in muscle lipid utilization, adipose energy storage, and gut fat absorption and possibly contributing to the pathogenesis of metabolic disorders, such as diabetes and obesity. On sensory cells, CD36 is involved in insect pheromone signaling and rodent fatty food preference. The signaling pathways downstream of CD36 involve ligand-dependent recruitment and activation of nonreceptor tyrosine kinases, specific mitogen-activated protein kinases, and the Vav family of guanine nucleotide exchange factors; modulation of focal adhesion constituents; and generation of intracellular reactive oxygen species. CD36 in many cells is localized in specialized cholesterol-rich membrane microdomains and may also interact with other membrane receptors, such as tetraspanins and integrins. Identification of the precise CD36 signaling pathways in specific cells elicited in response to specific ligands may yield novel targets for drug development.
CD36是一种存在于血小板、单核吞噬细胞、脂肪细胞、肝细胞、肌细胞和某些上皮细胞上的膜糖蛋白。在微血管内皮细胞上，CD36是血小板反应蛋白-1及相关蛋白的受体，作为血管生成的负调节因子发挥作用。在吞噬细胞上，CD36作为一种识别特定氧化磷脂和脂蛋白的清道夫受体，参与凋亡细胞、某些细菌和真菌病原体以及修饰的低密度脂蛋白的内化，从而促进炎症反应和动脉粥样血栓形成疾病。CD36还能结合长链脂肪酸并促进其转运进入细胞，从而参与肌肉脂质利用、脂肪能量储存和肠道脂肪吸收，可能还与代谢紊乱（如糖尿病和肥胖症）的发病机制有关。在感觉细胞上，CD36参与昆虫信息素信号传导和啮齿动物对高脂肪食物的偏好。CD36下游的信号通路包括配体依赖性募集和激活非受体酪氨酸激酶、特定的丝裂原活化蛋白激酶以及鸟嘌呤核苷酸交换因子的Vav家族；调节粘着斑成分；以及产生细胞内活性氧。许多细胞中的CD36定位于富含胆固醇的特殊膜微区，还可能与其他膜受体相互作用，如四跨膜蛋白和整合素。确定特定细胞中针对特定配体引发的精确CD36信号通路可能会产生新的药物开发靶点。
