Regulatory mechanism of CI^- transport via tyrosine phophorylation by cAMP

cAMP 酪氨酸磷酸化对 CI^- 转运的调节机制

• 批准号: 13670046
• 负责人: NIISATO Naomi
• 金额: $ 2.56万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670046/
• 关键词: Tyrosine phophorylation; CI^- transport; cAMP

We studied the regulatory mechanism of Samp-stimulated CI^- transport through tyrosime phosphorylation in renal epithelial A6 cells. Our results supported by a Grant-in-aid for Scientific Research (2001-2002) are summarized as follows.1.Camp is known to stimulate biphasic CI^- transport in renal epithelial A6 cells. Preteatment with tyrphostin A23 (a protein tyrosine kinase (PTK) inhibitor) abolished the Camp-stimulated CI^- transport by inhibiting the Na^+/K^+/2CI^- cotransporter. These results suggest that PTK is involved in regulation of the Na^+/K^+/2CI^- cotransporter in cAMP-stimulated CI^- transport2. Camp stimulation increased tyrosine phosphorylation in several proteins which was sensitive to tyrphotin A23, suggesting that these tyrosine phosphorylated proteins might contribute to regulate the Camp stimulation CI^- transport3. We examined whether Camp stimulation activates PTK by a change in plasma membrane tension. To increase plasma membrane tension by chlorpromazine also induced an increase in tyrosine phosphorylation of several proteins likely to Camp stimulationBased on these results, it is indicated that Camp stimulation increased tyrosine phophorylation of several proteins via cell volume-dependent changes in membrane tension, resulting in stimulation of CI^- transport in A6 cells

我们研究了samp刺激下肾上皮A6细胞通过酪氨酸磷酸化转运CI^-的调控机制。本文对2001-2002年度科研资助项目的研究成果进行了总结。已知Camp可刺激肾上皮A6细胞的双相CI^-转运。用tyrphostin A23（一种蛋白酪氨酸激酶（PTK）抑制剂）预处理通过抑制Na^+/K^+/2CI^-共转运体来消除camp刺激的CI^-运输。这些结果表明，PTK参与了camp刺激的CI^-转运t2中Na^+/K^+/2CI^-共转运体的调控。Camp刺激增加了几种对tyrphotin A23敏感的蛋白的酪氨酸磷酸化，表明这些酪氨酸磷酸化的蛋白可能有助于调节Camp刺激的CI^-转运。我们研究了Camp刺激是否通过改变质膜张力激活PTK。氯丙嗪增加质膜张力也诱导了几种可能受Camp刺激的蛋白酪氨酸磷酸化的增加。基于这些结果，表明Camp刺激通过细胞膜张力的细胞体积依赖性变化增加了几种蛋白酪氨酸磷酸化，从而刺激了A6细胞的CI^-运输

项目成果

Shinsaku Tokuda, Naomi Niisato: "Calmodulin-dependent regulation of hypotonicity-induced translocation of ENac in renal epithelial A6 cells"Biochem. Biophys. Res. Commun.. 298. 619-623 (2002)

Shinsaku Tokuda、Naomi Niisato：“肾上皮 A6 细胞中低渗诱导的 ENac 易位的钙调蛋白依赖性调节”Biochem。

Yoshinori Marunaka: "Effects of Ca^<2+> channel blockers on amiloride-sensitive Na^+-permeable channels and Na^+ transport in fetal rat alveolar type II epithelium"Biochemical Pharmacology. (in press). (2002)

Yoshinori Marunaka：“Ca ^ 2 通道阻滞剂对阿米洛利敏感的Na ^ -渗透通道和胎儿大鼠肺泡II型上皮细胞中Na ^ 转运的影响”生化药理学。

Naomi Niisato: "Activation of CFTR Cl^-channel by tyrphestins via a protein tyrosine kinase-independent pathway in forskolin-stimulated renal epithelial A6 cells"Life Sciences. (in press). (2002)

Naomi Niisato：“在毛喉素刺激的肾上皮 A6 细胞中，酪氨酸激酶通过蛋白酪氨酸激酶独立途径激活 CFTR Cl 通道”生命科学。

丸中良典: "肺組織におけるイオン輸送の制御"臨床呼吸生理. 33. 29-36 (2001)

Yoshinori Marunaka：“肺组织中离子传输的控制”临床呼吸生理学 33. 29-36 (2001)。

Niisato N, Marunaka Y: "Forskolin activation of apical Cl- channel and Na^+/K^+/2CI^- co transporter via a PTK-dependent pathway in renal epithelium"Biochem Biophys Res Commun. 285. 880-884 (2001)

Niisato N、Marunaka Y：“毛喉素通过肾上皮中 PTK 依赖性途径激活顶端 Cl-通道和 Na^/K^/2Cl^-co 转运蛋白”Biochem Biophys Res Commun。