现货供应p39 Antibody #3275

Specificity / Sensitivity

p39 Antibody detects endogenous levels of total p39 protein. p39抗体识别内源性的全部p39蛋白。

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic peptide surrounding Thr90 of human p39. Antibodies are purified by peptide affinity chromatography. 该多克隆抗体用与人类p39蛋白中Thr90附近氨基酸序列对应的人工合成肽段免疫动物而制成。该抗体使用蛋白亲和层析纯化而得。

Background

Cyclin-dependent kinases (CDKs) are serine/threonine kinases that are activated by cyclins and govern eukaryotic cell cycle progression. While CDK5 shares high sequence homology with its family members, it is thought mainly to function in postmitotic neurons, regulating the cytoarchitecture of these cells. Analogous to cyclins, p35 and p39 associate with and activate CDK5 despite the lack of sequence homology. CDK5 is ubiquitously expressed, but high levels of kinase activity are detected primarily in the nervous system due to the narrow expression pattern of p35 and p39 in post-mitotic neurons. A large number of CDK5 substrates have been identified although no discrete substrates have been attributed as a function of p35 vs. p39. Amongst many, substrates of CDK5 include p35 and p39. p35 is rapidly degraded (T1/2 <20 min) by the ubiquitin-proteasome pathway (1). However, p35 stability increases as CDK5 kinase activity decreases, and this is likely a result of decreased phosphorylation of p35 at Thr138 by CDK5 (2). NGF activates Erk and EGR1, and induces p35 expression in PC12 cells (3). Proteolytic cleavage of p35 by calpain produces p25 upon neurotoxic insult, resulting in prolonged activation of CDK5 by p25. Accumulation of p25 is found in neurodegenerative diseases such as Alzheimer's disease and Amyotrophic Lateral Sclerosis (ALS) (4-5). 细胞周期蛋白依赖性激酶（CDKs）是丝氨酸/苏氨酸激酶，它们被周期蛋白cyclins激活，控制真核细胞周期的进程。CDK5与其家庭成员分享同源性很高的序列，它被认为主要是在有丝分裂后的神经元中调节细胞结构。与周期蛋白cyclins类似，p35和p39与CDK5结合并激活CDK5，尽管它们缺乏序列同源性。CDK5是广泛表达的，但因为有丝分裂后神经元具有窄谱的表达P35和P39，其主要在中枢神经系统中具有高水平的激酶活性。大量CDK5的底物已被确定，虽然尚无某个分离的底物被归于P35或P39。在众多底物中，CDK5的底物包括p35和p39。p35被泛素 - 蛋白酶体途径迅速降解（T1/ 2 <20分钟）（1）。然而，P35的稳定性增加时CDK5激酶活性降低，可能是因为CDK5在P35的Thr138位点磷酸化水平减少所造成（2）。NGF激活Erk和EGR1，在PC12细胞中诱导p35表达（3）。毒性损害后calpain造成p35蛋白水解产生p25，导致CDK5长期被p25激活。P25积聚在神经退行性疾病如阿尔茨海默病和肌萎缩性侧索硬化症（ALS）中被发现（4-5）。

CDK5-null mice are perinatal lethal, whereas p35 or p39-null mice are viable. However, p35 and p39 double-null mutants display phenotypes identical to those of the CDK5-null mutant mice (6). Association of p39 but not p35 with CDK5 promotes Munc18-1 phosphorylation and Ca2+-dependent exocytosis (7). p39 binds to the actin cytoskeleton associated protein muskelin, and localizes to lamellipodia, fillopodia and growth cones of neurons (8,9). CDK5缺乏的小鼠在围产期就死亡，但P35或P39缺乏的小鼠能够存活。但是p35和p39同时突变缺乏的小鼠却与CDK5空白的突变小鼠具有相同的表型（6）。CDK5与P39而不是P35结合，可以促进Munc18-1的磷酸化和Ca2+依赖性的胞吐（7）。P39与肌动蛋白细胞骨架相关蛋白muskelin结合，定位神经元的板状伪足、丝状伪足和生长锥（8,9）。