GNA11
小结
GNA11是致癌基因，编码G蛋白复合体的一个亚基，是一种细胞内信号蛋白。G蛋白复合体可激活调节细胞生长和发育的细胞内的信号转导级联。GNA11编码一种G蛋白α亚基的特异Q类亚型。结合GTP的GNA11激活包括PLCγ的下游信号伴侣。通过第二信使生成，PLCγ激活PKC，激活MAPK信号级联，进而介导细胞增殖。GNA11的突变使蛋白质的GTPase活性失活，从而使GNA11在组成激活状态下与GTP保持结合，从而独立于激动剂与受体结合而扩增GPCR下游的信号。1%的皮肤黑色素瘤和36%的葡萄膜黑色素瘤中发现了GNA11的体细胞基因突变。在大约85%的葡萄膜黑色素瘤中发现了GNA11或GNAQ的互斥突变。
GNA11 gene encodes a subunit of the G-protein complex that activates intracellular signaling cascades which regulate cell growth and development. G-protein Coupled Receptors (GPCRs) are transmembrane complexes comprising seven domains and are activated by a variety of agonists (e.g., lipids or small proteins), depending on the GPCR type. Upon activation, a conformational change facilitates activation of membrane-bound, intracellular heterotrimeric G proteins, which are composed of three subunits (α, β, γ). The G-protein is decoupled into active G-alpha and G-beta-gamma subunits, which are released from the agonist-activated GPCR and participate in various intracellular signaling pathways; G protein activation may also occur independently of GPCR. The G-alpha subunit, bound to GDP when inactive, exchanges GDP for GTP in the activated state. GNA11 encodes a specific q-class subtype of the G-protein alpha subunit. GTP-bound GNA11 activates downstream signaling partners, which include PLCγ. Via secondary messenger generation, PLCγ activates PKC, which activates the MAPK signaling cascade, which in turn mediates cell proliferation. Mutations of GNA11 inactivate the GTPase activity of the protein, thereby causing GNA11 to remain bound to GTP in a constitutively activated state, which consequently amplifies the signaling downstream of the GPCR independent of agonist binding to the receptor. Somatic gene mutations in GNA11 specifically are noted in 1% of cutaneous melanoma and 36% of uveal melanomas. Mutually exclusive mutations of either GNA11 or GNAQ have been found in approximately 85% of uveal melanomas.