Endocytosis at the apical plasma membrane of pancreatic acinar cells is regulated by tyrosine kinases
Endocytosis at the apical plasma membrane of pancreatic acinar cells is regulated by tyrosine kinases
复制标题
DOI：
10.1152/ajpcell.1999.276.2.c306
复制
发表时间：
1999-02-01
影响因子：
5.5
通讯作者：
Gelrud, A
中科院分区：
文献类型：
--
作者：
Freedman, SD;Katz, MH;Gelrud, A
我们已经证明，胰腺腺泡细胞顶端质膜的内吞作用受腺泡管腔的pH调节，并与糖基磷脂酰肌醇锚定蛋白GP2的切割有关。这项研究的目的是确定激活内吞作用的转导途径。大鼠胰腺腺泡细胞顶端内吞作用的研究是通过预先用缩胆囊素刺激，然后测量辣根过氧化物酶(HRP)摄取。镧、星形孢子素和Forsklin对HRP摄取无影响。细胞松弛素D显著抑制内吞作用，表明其依赖于肌动蛋白细丝的完整性。金雀异黄素和特异性酪氨酸蛋白抑制剂B42也抑制HRP的摄取，暗示酪氨酸激酶参与了HRP摄取的调节。在使用Src激酶特异性底物的情况下，Src激酶活性与内吞作用的激活在时间上是相关的。大鼠和小鼠胰腺腺泡中85 kDa底物酪氨酸依赖的磷酸化与Src激酶的激活和对HRP摄取的依赖于pa的调节相关。这些结果表明，腺泡细胞的顶端内吞作用与酪氨酸激酶的激活有关，并依赖于肌动蛋白细胞骨架。
We have shown that endocytosis at the apical plasma membrane of pancreatic acinar cells is regulated by the pH of the acinar lumen and is associated with cleavage of GP2, a glycosyl phosphatidylinositol-anchored protein. The aim of this study was to determine the transduction pathway by which endocytosis is activated. Apical endocytosis was studied in rat pancreatic acini by prestimulation with cholecystokinin followed by measurement of horseradish peroxidase (HRP) uptake. Lanthanum, staurosporine, and forskolin had no effect on HRP uptake. Cytochalasin D significantly inhibited endocytosis, indicating a dependence on actin filament integrity. Genistein and the specific tyrphostin inhibitor B42 also inhibited HRP uptake, implicating tyrosine kinases in the regulation of HRP uptake. With the use of an Src kinase-specific substrate, Src kinase activity was temporally related to activation of endocytosis. The tyrosine-dependent phosphorylation of an 85-kDa substrate in both rat; and mouse pancreatic acini correlated with Src kinase activation and pa-dependent regulation of HRP uptake. These results indicate that apical endocytosis in acinar cells is associated with tyrosine kinase activation and is dependent on the actin cytoskeleton.