PRKAR1A编码蛋白是一种环腺苷单磷酸(cAMP)依赖的调节亚基,其抑制蛋白激酶A(PKA)的催化亚基。cAMP与调控亚基PRKAR1A的结合释放PKA的催化亚基以磷酸化靶蛋白,导致促进细胞增殖、细胞分裂和侵袭的信号通路的激活。PRKAR1A的胚系突变导致Carney复合症,其特征为皮肤色素性病变、粘液瘤、胶原瘤和纤维瘤,以及导致Cushing综合征的原发性色素性结节性肾上腺皮质疾病。在肾上腺皮质肿瘤中鉴定了PRKAR1A的缺失和功能丧失性突变。错义和无义突变导致PKA催化亚基的cAMP依赖性解离减少,提示PRKAR1A起肿瘤抑制作用。在急性早幼粒细胞白血病中和LA乳头状甲状腺癌中, PRARK1A是RARA发生易位的伴侣基因。
PRKAR1A is a cyclic adenosine monophosphate (cAMP)-dependent regulatory subunit that inhibits the catalytic subunits of protein kinase A (PKA). Binding of cAMP to the regulatory subunit PRKAR1A releases the catalytic subunits of PKA to phosphorylate target proteins, resulting in the activation of signaling pathways that promote cell proliferation, cell division and invasion. Germline mutations in PRKAR1A are responsible for the Carney complex disorder characterized by skin pigmented lesions, myxomas, collagenomas and fibromas and for primary pigmented nodular adrenocortical disease leading to Cushing's syndrome. Deletions and loss-of-function mutations in PRKAR1A have been identified in adrenocortical tumors. Missense and nonsense mutations result in decreased cAMP-dependent dissociation of PKA catalytic subunits, suggesting that PRKAR1A functions as a tumor suppressor. PRKAR1A has been identified as a translocation partner for RARA in acute promyelocytic leukemia and for RET in papillary thyroid carcinoma.
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