PRKAR2A(蛋白激酶cAMP依赖性调节亚基IIα)是cAMP依赖性蛋白激酶(PKA)的一个关键调节亚基,属于PKA调节亚基家族(PRKAR家族)。PKA是一种重要的丝氨酸/苏氨酸激酶,通过cAMP信号通路参与多种细胞过程的调控,包括代谢、基因表达、细胞增殖和分化等。PRKAR2A与PRKAR1A、PRKAR1B和PRKAR2B共同组成PKA的调节亚基家族,它们的主要功能是与催化亚基结合并抑制其活性,直到cAMP水平升高导致调节亚基解离,从而激活PKA。PRKAR2A主要在神经系统、心脏和骨骼肌中高表达,其特点是与其他调节亚基相比具有更高的cAMP结合亲和力,这使得它在特定组织中能更敏感地响应cAMP信号。PRKAR2A的突变或表达异常与多种疾病相关,包括心脏疾病、内分泌肿瘤(如Carney复合征)和神经系统疾病。Carney复合征是一种罕见的遗传性疾病,主要由PRKAR1A突变引起,但PRKAR2A的异常表达也可能参与其中。PRKAR2A的突变可能导致PKA信号通路的异常激活或抑制,进而影响细胞增殖和分化,促进肿瘤发生。PRKAR2A过表达可能导致PKA活性持续升高,扰乱正常的cAMP信号传导,影响细胞代谢和生长,甚至促进肿瘤发展。相反,PRKAR2A表达降低可能导致PKA活性不足,影响细胞对cAMP信号的响应,进而干扰正常的生理功能,如心脏收缩或神经传导。PRKAR2A还与其他基因和蛋白相互作用,例如与AKAPs(A激酶锚定蛋白)结合,帮助PKA定位到特定亚细胞区域,确保信号通路的精确调控。PRKAR2A的表达水平变化还可能影响其他下游基因的表达,如CREB(cAMP反应元件结合蛋白),从而进一步影响细胞功能。PRKAR2A所在的PRKAR基因家族成员均具有高度保守的cAMP结合域和二聚化域,能够形成同源或异源二聚体,并与PKA催化亚基结合。家族成员的共性是参与cAMP-PKA信号通路的调控,但不同亚基的表达模式和功能存在组织特异性差异。PRKAR2A在维持正常生理功能和疾病发生中扮演重要角色,其表达和活性的精确调控对细胞稳态至关重要。
cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activating the cAMP-dependent protein kinase, which transduces the signal through phosphorylation of different target proteins. The inactive kinase holoenzyme is a tetramer composed of two regulatory and two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. Four different regulatory subunits and three catalytic subunits have been identified in humans. The protein encoded by this gene is one of the regulatory subunits. This subunit can be phosphorylated by the activated catalytic subunit. It may interact with various A-kinase anchoring proteins and determine the subcellular localization of cAMP-dependent protein kinase. This subunit has been shown to regulate protein transport from endosomes to the Golgi apparatus and further to the endoplasmic reticulum (ER). [provided by RefSeq, Jul 2008]
cAMP的是一个信号分子对各种细胞功能很重要的。 cAMP的施加通过激活cAMP依赖性蛋白激酶,其通过不同的靶蛋白的磷酸化将信号传递其作用。非活动激酶全酶是两个调控和两个催化亚基组成的四聚体。的cAMP导致非活动全酶的解离成结合到四个cAMP和两个自由单体催化亚基调节亚基的二聚体。四种不同的调节亚基和三个催化亚基在人类已确定。由该基因编码的蛋白质是调节亚基中的一个。此亚基可由活化的催化亚基被磷酸化。它可以与各种A-激酶锚定蛋白相互作用,并确定cAMP依赖性蛋白激酶的亚细胞定位。这个亚基已经显示从内涵体到高尔基体蛋白运输和进一步调节至内质网(ER)。 [由RefSeq的,2008年7月提供]
PRKAR2A基因(以及对应的蛋白质)的细胞分布位置:
PRKAR2A基因的本体(GO)信息:
| 名称 |
|---|
| 4210 Apoptosis [PATH:hsa04210] |
| 4910 Insulin signaling pathway [PATH:hsa04910] |
| 名称 |
|---|
| Aquaporin-mediated transport |
| Ca-dependent events |
| Calmodulin induced events |
| CaM pathway |
| DAG and IP3 signaling |
| DAP12 interactions |
| DAP12 signaling |
| DARPP-32 events |
| Downstream signal transduction |
| Downstream signaling of activated FGFR1 |
| Downstream signaling of activated FGFR2 |
| Downstream signaling of activated FGFR3 |
| Downstream signaling of activated FGFR4 |
| EGFR interacts with phospholipase C-gamma |
| Factors involved in megakaryocyte development and platelet production |
| G-protein mediated events |
| Glucagon signaling in metabolic regulation |
| Glucagon-like Peptide-1 (GLP1) regulates insulin secretion |
| Hedgehog 'off' state |
| Hemostasis |
| Immune System |
| Innate Immune System |
| Integration of energy metabolism |
| NGF signalling via TRKA from the plasma membrane |
| Opioid Signalling |
| Phospholipase C-mediated cascade; FGFR2 |
| Phospholipase C-mediated cascade; FGFR3 |
| Phospholipase C-mediated cascade; FGFR4 |
| Phospholipase C-mediated cascade: FGFR1 |
| PKA activation |
| PKA activation in glucagon signalling |
| PKA-mediated phosphorylation of CREB |
| PLC beta mediated events |
| PLC-gamma1 signalling |
| PLCG1 events in ERBB2 signaling |
| Regulation of insulin secretion |
| Signaling by EGFR |
| Signaling by ERBB2 |
| Signaling by FGFR |
| Signaling by FGFR1 |
| Signaling by FGFR2 |
| Signaling by FGFR3 |
| Signaling by FGFR4 |
| Signaling by GPCR |
| Signaling by Hedgehog |
| Signaling by PDGF |
| Signalling by NGF |
| Transmembrane transport of small molecules |
| Vasopressin regulates renal water homeostasis via Aquaporins |
| 疾病名称 | 关系值 | NofPmids | NofSnps | 来源 |
| Schizophrenia | 0.002367032 | 1 | 0 | GAD |
| Pituitary Diseases | 0.000271442 | 1 | 0 | BeFree |
| Prostate carcinoma | 0.000271442 | 1 | 0 | BeFree |
| Congenital Abnormality | 0.000271442 | 1 | 0 | BeFree |
| Malignant neoplasm of prostate | 0.000271442 | 1 | 0 | BeFree |
| Kallmann Syndrome | 0.000271442 | 1 | 0 | BeFree |
| Kallmann Syndrome 1 | 0.000271442 | 1 | 0 | BeFree |
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