NRG1 Q02297

膜结合型神经调节蛋白-1前体 (Pro-NRG1) [裂解为：神经调节蛋白-1 (乙酰胆碱受体诱导活性) (ARIA) (乳腺癌细胞分化因子 p45) (神经胶质生长因子) (Heregulin) (HRG) (Neu分化因子) (感觉和运动神经元衍生因子)]

功能描述

ERBB3和ERBB4酪氨酸激酶受体的直接配体。同时募集ERBB1和ERBB2共受体，导致配体刺激的酪氨酸磷酸化和ERBB受体的激活。多种同工异构体执行不同的功能，例如诱导上皮细胞、神经胶质细胞、神经元和骨骼肌细胞的生长和分化；在神经肌肉接头形成过程中诱导突触囊泡中乙酰胆碱受体的表达；刺激乳腺小叶肺泡出芽和乳汁产生并诱导乳腺肿瘤细胞分化；刺激施万细胞增殖；参与心肌发育，例如发育中心脏的小梁形成。Isoform 10可能在运动和感觉神经元发育中起作用。结合ERBB4 (PubMed:10867024, PubMed:7902537)。结合ERBB3 (PubMed:20682778)。作为整合素的配体，并（通过EGF结构域）结合整合素ITGAV:ITGB3或ITGA6:ITGB4。其与整合素的结合以及随后与整合素和ERBB3形成的三元复合物对于NRG1-ERBB信号传导至关重要。诱导MAPK3/ERK1、MAPK1/ERK2和AKT1的磷酸化和激活 (PubMed:20682778)。配体依赖性的ERBB4内吞作用对于神经元中NRG1介导的这些激酶的激活至关重要 (By similarity)。 {ECO:0000250|UniProtKB:P43322, ECO:0000269|PubMed:10867024, ECO:0000269|PubMed:1348215, ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:7902537}。

组织特异性

Type I isoforms are the predominant forms expressed in the endocardium. Isoform alpha is expressed in breast, ovary, testis, prostate, heart, skeletal muscle, lung, placenta liver, kidney, salivary gland, small intestine and brain, but not in uterus, stomach, pancreas, and spleen. Isoform 3 is the predominant form in mesenchymal cells and in non-neuronal organs, whereas isoform 6 is the major neuronal form. Isoform 8 is expressed in spinal cord and brain. Isoform 9 is the major form in skeletal muscle cells; in the nervous system it is expressed in spinal cord and brain. Also detected in adult heart, placenta, lung, liver, kidney, and pancreas. Isoform 10 is expressed in nervous system: spinal cord motor neurons, dorsal root ganglion neurons, and brain. Predominant isoform expressed in sensory and motor neurons. Not detected in adult heart, placenta, lung, liver, skeletal muscle, kidney, and pancreas. Not expressed in fetal lung, liver and kidney. Type IV isoforms are brain-specific.

亚细胞定位

[Pro-neuregulin-1, membrane-bound isoform]: Cell membrane; Single-pass type I membrane protein. Note=Does not seem to be active.; SUBCELLULAR LOCATION: [Neuregulin-1]: Secreted.; SUBCELLULAR LOCATION: [Isoform 8]: Nucleus. Note=May be nuclear.; SUBCELLULAR LOCATION: [Isoform 9]: Secreted. Note=Has a signal peptide.; SUBCELLULAR LOCATION: [Isoform 10]: Membrane; Single-pass type I membrane protein. Note=May possess an internal uncleaved signal sequence.