Protein Kinase C-mediated Integrin Activation

蛋白激酶 C 介导的整合素激活

• 批准号: 6778181
• 负责人: Jianxun LI
• 金额: $ 23.38万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6778181
• 关键词: actin binding protein; biological signal transduction; calmodulin; cell membrane; cytoskeletal proteins; cytoskeleton; enzyme substrate complex; fluorescence resonance energy transfer; integrins; intermolecular interaction; leukocyte adhesion molecules; leukocytes; membrane proteins; microtubule associated protein; molecular assembly /self assembly; phosphorylation; protein binding; protein degradation; protein kinase C; protein localization; protein purification; protein structure function; site directed mutagenesis; tissue /cell culture

DESCRIPTION (provided by applicant): In resting leukocytes, B2 integrin molecules are immobilized on the cell membrane in a diffused distribution, because they are constrained by cytoskeletal complex. Activation signals through the "inside-out" pathway cause this cytoskeletal complex to dissociate, resulting in enhanced free motion and clustering of f32 integrin. The clustered integrin provides high avidity binding to the ligands. The goal of this proposal is to identify and characterize the cytoskeletal complex constraining the integrin molecules in resting leukocytes, termed "preactivation cytoskeletal complex" in this proposal. Using the ability of regulating molecular mobility and clustering of B2 integrin as the criteria, we propose to determine whether talin, calmodulin, and dynamitin - three proteins involved in integrin activation-are members of the preactivation complex. Since integrin activation should not be a "none" or "all" process, two quantitative assays will be introduced: the single particle tracking method to quantitate the molecular mobility of B2 integrin and the fluorescent resonance energy transfer method to quantitate the clustering. Once we have identified the new members of the preactivation complex, their interrelationship with the currently known members, i.e. PKC, MacMARCKS, actin, and microtubule filaments, and among themselves will be determined by individually disrupting the function of each one by mutagenesis or by specific inhibitors. The significance of these studies is two-fold: if these proteins are indeed members of the preactivation complex, then the currently understood sequence of integrin activation is confirmed and we will have found new members. On the other hand, if these proteins regulate integrin activation without changing integrin mobility and clustering, then the currently held scheme of integrin activation requires modification. Information obtained from this study will provide a new understanding of the role of cytoskeletal proteins in regulating integrin activation. Since B2 integrin is a crucial regulator of the immune function in health and in diseases, this proposal has broad significance for clinical medicine.

描述（由申请人提供）：在静息白细胞中，B2整合素

项目成果

Macrophage-enriched myristoylated alanine-rich C kinase substrate and its phosphorylation is required for the phorbol ester-stimulated diffusion of beta 2 integrin molecules.

富含巨噬细胞的肉豆蔻酰化富含丙氨酸的 C 激酶底物及其磷酸化是佛波酯刺激的 β2 整联蛋白分子扩散所必需的。

• DOI: 10.1074/jbc.m909129199
• 发表时间: 2000
• 期刊: The Journal of biological chemistry
• 作者: Zhou,X;Li,J
• 通讯作者: Li,J

In vivo interaction between dynamitin and MacMARCKS detected by the fluorescent resonance energy transfer method.

通过荧光共振能量转移方法检测动力蛋白和 MacMARCKS 之间的体内相互作用。

• DOI: 10.1074/jbc.m010513200
• 发表时间: 2001
• 期刊: The Journal of biological chemistry
• 作者: Jin,T;Yue,L;Li,J
• 通讯作者: Li,J

Expression of MacMARCKS restores cell adhesion to ICAM-1-coated surface.

MacMARCKS 的表达可恢复细胞对 ICAM-1 包被表面的粘附。

• DOI: 10.3109/15419060009109018
• 发表时间: 2000
• 期刊: Cell adhesion and communication
• 作者: Yue,L;Bao,Z;Li,J
• 通讯作者: Li,J