Convergence of cell cycle regulation and growth factor signals on GRASP65
Convergence of cell cycle regulation and growth factor signals on GRASP65
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DOI：
10.1074/jbc.m502442200
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发表时间：
2005-06-17
影响因子：
4.8
通讯作者：
Nakamura, N
中科院分区：
文献类型：
--
作者：
Yoshimura, S;Yoshioka, K;Nakamura, N
GRASP 65与其他高尔基体基质成分一起，有助于高尔基体池在间期细胞中的堆积。在有丝分裂期间，GRASP 65被严重磷酸化，并且反过来，池堆积被抑制，导致高尔基体的分解。在这里，我们表明，GRASP 65是磷酸化的丝氨酸277在间期细胞，这是强烈增强响应添加血清或表皮生长因子。这是由ERK直接介导的，表明GRASP 65在生长因子信号转导中具有一定作用。在有丝分裂过程中，Ser-277的磷酸化也显著增加，但这是由Cdk 1介导的，而不是由ERK介导的。将不含N-末端豆蔻酰化的重组GRASP 65或含有Ser-277的肽片段显微注射到正常大鼠肾细胞的胞质溶胶中抑制通过有丝分裂。当Ser-277被丙氨酸取代时，这种作用被消除，表明Ser-277的磷酸化在细胞周期调节中起重要作用。细胞周期调控和生长因子信号在GRASP 65 Ser-277上的汇聚表明GRASP 65可能是控制细胞生长的信号整合者。
Together with other Golgi matrix components, GRASP65 contributes to the stacking of Golgi cisternae in interphase cells. During mitosis, GRASP65 is heavily phosphorylated, and in turn, cisternal stacking is inhibited leading to the breakdown of the Golgi apparatus. Here we show that GRASP65 is phosphorylated on serine 277 in interphase cells, and this is strongly enhanced in response to the addition of serum or epidermal growth factor. This is directly mediated by ERK suggesting that GRASP65 has some role in growth factor signal transduction. Phosphorylation of Ser-277 is also dramatically increased during mitosis, however this is mediated by Cdk1 and not by ERK. The microinjection of recombinant GRASP65 without N-terminal myristoylation or a peptide fragment containing Ser-277 into the cytosol of normal rat kidney cells inhibits passage through mitosis. This effect is abolished when Ser-277 is replaced with alanine suggesting the phosphorylation of Ser-277 plays an important role in cell cycle regulation. The convergence of cell cycle regulation and growth factor signals on GRASP65 Ser-277 suggests that GRASP65 may function as a signal integrator controlling the cell growth.