Futter Marie, Uematsu Ken, Bullock Stewart A, Kim Yong, Hemmings Hugh C, Nishi Akinori, Greengard Paul, Nairn Angus C
Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021, USA.
Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3489-94. doi: 10.1073/pnas.0409802102. Epub 2005 Feb 22.
Spinophilin is a protein that binds to protein phosphatase-1 and actin and modulates excitatory synaptic transmission and dendritic spine morphology. We have identified three sites phosphorylated by ERK2 (Ser-15 and Ser-205) and cyclin-dependent PK 5 (Cdk5) (Ser-17), within the actin-binding domain of spinophilin. Cdk5 and ERK2 both phosphorylated spinophilin in intact cells. However, in vitro, phosphorylation by ERK2, but not by Cdk5, was able to modulate the ability of spinophilin to bind to and bundle actin filaments. In neurons and HEK293 cells expressing GFP-tagged variants of spinophilin, imaging studies demonstrated that introduction of a phospho-site mimic (Ser-15 to glutamate) was associated with increased filopodial density. These results support a role for spinophilin phosphorylation by ERK2 in the regulation of spine morphogenesis.
亲嗜素是一种与蛋白磷酸酶-1和肌动蛋白结合的蛋白质，可调节兴奋性突触传递和树突棘形态。我们已经在亲嗜素的肌动蛋白结合域内鉴定出三个被细胞外信号调节激酶2（ERK2）（丝氨酸-15和丝氨酸-205）和细胞周期蛋白依赖性蛋白激酶5（Cdk5）（丝氨酸-17）磷酸化的位点。Cdk5和ERK2都能在完整细胞中使亲嗜素磷酸化。然而，在体外，ERK2介导的磷酸化而非Cdk5介导的磷酸化能够调节亲嗜素结合和捆绑肌动蛋白丝的能力。在表达绿色荧光蛋白标记的亲嗜素变体的神经元和人胚肾293细胞中，成像研究表明，引入磷酸化位点模拟物（丝氨酸-15突变为谷氨酸）与丝状伪足密度增加有关。这些结果支持ERK2介导的亲嗜素磷酸化在脊柱形态发生调节中的作用。
