Structure, Function and Regulation of Protein Kinase C

蛋白激酶C的结构、功能和调控

基本信息

批准号：
9067372
负责人：
ALEXANDRA C. NEWTON
金额：
$ 42.16万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-12-01 至 2017-05-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The long-term goal of this proposal is to understand the molecular and cellular mechanisms of protein kinase C and how these mechanisms are altered by cancer-associated mutations in members of this enzyme family to promote oncogenesis. Protein kinase C isozymes transduce the myriad of signals resulting from receptor-mediated hydrolysis of phospholipids, playing critical roles in diverse cellular functions The discovery in the 1980s that they are the receptors for the potent tumor promoting phorbol esters, led to the dogma that activation of protein kinase C by phorbol esters promotes tumorigenesis. However, the finding that long-term treatment with phorbol esters causes the degradation of protein kinase C opens this interpretation to question. Protein kinase C levels are aberrant in diverse cancers, and over 160 mutations in protein kinase C isozymes have been found in human cancers. However, whether protein kinase C isozymes function as tumor suppressors or oncogenes is not established. By understanding the molecular and cellular mechanisms of protein kinase C, and taking advantage of novel tools our lab has developed, we are poised to address this fundamental question. Thus, a central hypothesis driving this proposal is that protein kinase C may be a tumor suppressor, with inactivation (rather than activation, as is the dogma) of the kinase promoting oncogenic pathways. Three Aims are proposed: 1] to advance knowledge on the molecular mechanisms of protein kinase C, 2] to understand protein kinase C signaling in cells, and 3] to examine how cancer-associated mutations in protein kinase C alter its function, testing the hypothesis that protein kinase C may be a tumor suppressor rather than oncogene.

描述（由申请人提供）：该提案的长期目标是了解蛋白激酶C的分子和细胞机制，以及该酶家族成员中与癌症相关的突变改变这些机制，以促进肿瘤发生。 Protein kinase C isozymes transduce the myriad of signals resulting from receptor-mediated hydrolysis of phospholipids, playing critical roles in diverse cellular functions The discovery in the 1980s that they are the receptors for the potent tumor promoting phorbol esters, led to the dogma that activation of protein kinase C by phorbol esters promotes tumorigenesis.然而，发现用佛波酯长期治疗导致蛋白激酶C的降解的发现为问题开辟了这种解释。蛋白激酶C水平在各种癌症中异常，并且在人类癌症中发现了蛋白激酶C同工酶中160多个突变。但是，尚未确定蛋白激酶C同工酶作为肿瘤抑制剂还是癌基因的作用。通过了解蛋白激酶C的分子和细胞机制，并利用实验室开发的新工具，我们准备解决这个基本问题。因此，推动该建议的中心假设是蛋白激酶C可能是肿瘤抑制因子，具有促进致癌途径的激酶的失活（而不是激活）。提出了三个目的：1]促进有关蛋白激酶C，2]的分子机制的知识，以了解细胞中的蛋白激酶C信号传导，以及3]，以检查蛋白激酶C中癌症相关的突变如何改变其功能，检验蛋白激酶C可能是肿瘤抑制者而不是肿瘤的假说。

项目成果

期刊论文数量（83）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Protein kinase C as a tumor suppressor.

DOI：
10.1016/j.semcancer.2017.04.017
发表时间：
2018-03
期刊：
Seminars in cancer biology
影响因子：
14.5
作者：
Newton AC
通讯作者：
Newton AC

Calcium-independent binding to interfacial phorbol esters causes protein kinase C to associate with membranes in the absence of acidic lipids.

与界面佛波酯的钙独立结合导致蛋白激酶 C 在没有酸性脂质的情况下与膜结合。

DOI：
10.1021/bi952031q
发表时间：
1996
期刊：
Biochemistry.
影响因子：
0
作者：
Mosior,M;Newton,AC
通讯作者：
Newton,AC

Mechanism of the apparent cooperativity in the interaction of protein kinase C with phosphatidylserine.

蛋白激酶C与磷脂酰丝氨酸相互作用的明显协同机制。

DOI：
10.1021/bi981344t
发表时间：
1998
期刊：
Biochemistry.
影响因子：
0
作者：
Mosior,M;Newton,AC
通讯作者：
Newton,AC

Protein kinase C beta II suppresses colorectal cancer by regulating IGF-1 mediated cell survival.

DOI：
10.18632/oncotarget.8062
发表时间：
2016-04-12
期刊：
Oncotarget
影响因子：
0
作者：
Dowling CM;Phelan J;Callender JA;Cathcart MC;Mehigan B;McCormick P;Dalton T;Coffey JC;Newton AC;O'Sullivan J;Kiely PA
通讯作者：
Kiely PA

Isozyme-specific inhibition of protein kinase C by RNA aptamers.