The phosphorylation of CapZ-interacting protein (CapZIP) by stress-activated protein kinases triggers its dissociation from CapZ
The phosphorylation of CapZ-interacting protein (CapZIP) by stress-activated protein kinases triggers its dissociation from CapZ
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DOI：
10.1042/bj20050387
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发表时间：
2005-07-01
影响因子：
4.1
通讯作者：
Cohen, P
中科院分区：
文献类型：
--
作者：
Eyers, CE;McNeill, H;Cohen, P
在肌肉提取物中检测到一种在免疫细胞和肌肉中表达的蛋白质，作为几种 SAPK（应激激活蛋白激酶）的底物。它与脾细胞中的 F-肌动蛋白加帽蛋白 CapZ 特异性相互作用，因此被称为“CapZIP”（CapZ 相互作用蛋白）。在体外，人 CapZIP 在 Ser-179 和 Ser-244 处被 MAPKAP-K2（丝裂原激活蛋白激酶激活蛋白激酶 2）或 MAPKAP-K3 磷酸化。 Anisomycin 诱导 Jurkat 细胞中 CapZIP Ser-179 的磷酸化，而 SB 203580 可以阻止这种磷酸化，这与 MAPKAP-K2 和/或 MAPKAP-K3 的磷酸化一致。然而，渗透压休克诱导的 Set-179 磷酸化不受 SB 203580 的影响。这些和其他结果表明，CapZIP 在细胞中的 Ser-179 位置被 MAPKAP-K2/MAPKAP-K3 和至少一种其他蛋白激酶磷酸化。应激激活的 MAP 激酶家族成员在许多位点磷酸化人 CapZIP，包括 Ser-68、Ser-83、Ser-108 和 Ser-216。当 Jurkat 细胞暴露于渗透压休克时，Ser-108 被磷酸化，而渗透压休克不受 SB 203580 和/或 PD 184352 的影响，或者在不表达 SAPK3/p38 gamma 或 SAPK4/p38 delta 的小鼠脾细胞中。我们的结果表明 CapZIP 可能被 JNK（c-Jun N 末端激酶）磷酸化，在体外几分钟内将 CapZIP 磷酸化至 > 5 mol/mol。渗透压休克或茴香霉素触发 Jurkat 细胞中 CapZIP 从 CapZ 解离，表明 CapZIP 磷酸化可能调节 CapZ 在体内重塑肌动蛋白丝组装的能力。
A protein expressed in immune cells and muscle was detected in muscle extracts as a substrate for several SAPKs (stress-activated protein kinases). It interacted specifically with the F-actin capping protein CapZ in splenocytes, and was therefore termed 'CapZIP' (CapZ-interacting protein). Human CapZIP was phosphorylated at Ser-179 and Ser-244 by MAPKAP-K2 (mitogen-activated protein kinase-activated protein kinase 2) or MAPKAP-K3 in vitro. Anisomycin induced the phosphorylation of CapZIP at Ser-179 in Jurkat cells, which was prevented by SB 203580, consistent with phosphorylation by MAPKAP-K2 and/or MAPKAP-K3. However, osmotic shock-induced phosphorylation of Set-179 was unaffected by SB 203580. These and other results suggest that CapZIP is phosphorylated at Ser-179 in cells by MAPKAP-K2/MAPKAP-K3, and at least one other protein kinase. Stress-activated MAP kinase family members phosphorylated human CapZIP at many sites, including Ser-68, Ser-83, Ser-108 and Ser-216. Ser-108 became phosphorylated when Jurkat cells were exposed to osmotic shock, which was unaffected by SB 203580 and/or PD 184352, or in splenocytes from mice that do not express either SAPK3/p38 gamma or SAPK4/p38 delta. Our results suggest that CapZIP may be phosphorylated by JNK (c-Jun N-terminal kinase), which phosphorylates CapZIP to > 5 mol/mol within minutes in vitro. Osmotic shock or anisomycin triggered the dissociation of CapZIP from CapZ in Jurkat cells, suggesting that phosphorylation of CapZIP may regulate the ability of CapZ to remodel actin filament assembly in vivo.