FUNCTION OF C-SRC AND RELATED KINASES IN CHROMAFFIN CELLS

C-SRC 及相关激酶在嗜铬细胞中的功能

基本信息

  • 批准号:
    6311495
  • 负责人:
  • 金额:
    $ 1.8万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2000
  • 资助国家:
    美国
  • 起止时间:
    2000-05-01 至 2001-04-30
  • 项目状态:
    已结题

项目摘要

Pp60c-src is a 60 kDa nonreceptor tyrosine protein kinase that is found in highest concentrations in non-dividing cells specialized for exocytosis, such as adrenal chromaffin cells. Accumulation in post- mitotic cells is an unexpected finding, considering the popularly held notion that pp60c-src, by analogy with its viral transforming counterpart, pp60v-src, is considered to play a role in control of cellular proliferation. The overall goal of our studies is to elucidate the function(s) of pp60c-src and related kinases in normal cells in which they are found to be naturally abundant. Several lines of evidence indicate that pp60c-src plays a role in the secretory process of chromaffin cells. They include (a) the subcellular localization of pp60c-src to the secretory vesicle (chromaffin granule) membrane, (b) modulation of pp60c-src specific tyrosine kinase activity following secretagogue stimulation, and (c) enhanced secretory activity of cultured chromaffin cells that transiently overexpress c-src using vaccinia virus vectors. Surprisingly, overexpression of a kinase-defective c-src also enhances secretory activity, suggesting that at least part of the effect of ectopically-expressed c-src on secretion is mediated through the N- terminal regulatory domain of the molecule. However, the changes in phosphotyrosine content of cellular proteins, as well as the modulations of c-src kinase activity which occur following secretagogue treatment, indicate that the C-terminal catalytic domain may also be important for the effect of pp60c-src on secretion. The goals of this proposal, therefore, are to identify and characterize cellular proteins that interact with pp60c-src, either as regulators or substrates, and to determine which subdomains of pp60c-src bind these proteins and are responsible for src's effect in viral-mediated overexpression studies. This will be accomplished by (a) screening a panel of available antibodies for their ability to react with proteins that co-precipitate with src protein or domains of pp60c-src (b) purifying novel proteins that co-precipitate with either intact pp60c-src or domains of pp60c-src, and (c) generating monoclonal antibodies to unidentified substrates of tyrosine kinases in chromaffin cells, using phosphotyrosine immunoaffinity reagents to purify them. Identified proteins will be characterized with respect to their relationship with pp60c-src and their function in chromaffin cells. Immunologic and genetic reagents for selected proteins will be generated to facilitate these studies. Which N-terminal domains of pp60c-src are responsible for the enhanced secretory activity will be further investigated using viral expression vectors and correlated with the binding of specific proteins. Similar studies will be initiated with pp62c-yes and pp59fyn to test the degree of functional overlap between the different src family members. Through these studies we hope to clarify the mechanism by which pp60c-src and related kinases participate in chromaffin cell biology.
Pp60c-src是一种60 kDa的非受体酪氨酸蛋白激酶

项目成果

期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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SARAH J PARSONS其他文献

SARAH J PARSONS的其他文献

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{{ truncateString('SARAH J PARSONS', 18)}}的其他基金

Neuroendocrine Cells in Prostate Cancer
前列腺癌中的神经内分泌细胞
  • 批准号:
    7728880
  • 财政年份:
    2008
  • 资助金额:
    $ 1.8万
  • 项目类别:
c-Src/EGF Receptors Interactions and Therapeutic Resistance in Breast Cancer
乳腺癌中的 c-Src/EGF 受体相互作用和治疗耐药
  • 批准号:
    7254940
  • 财政年份:
    2006
  • 资助金额:
    $ 1.8万
  • 项目类别:
c-Src/EGF Receptors Interactions and Therapeutic Resistance in Breast Cancer
乳腺癌中的 c-Src/EGF 受体相互作用和治疗耐药
  • 批准号:
    7629190
  • 财政年份:
    2006
  • 资助金额:
    $ 1.8万
  • 项目类别:
c-Src/EGF Receptors Interactions and Therapeutic Resistance in Breast Cancer
乳腺癌中的 c-Src/EGF 受体相互作用和治疗耐药
  • 批准号:
    7428876
  • 财政年份:
    2006
  • 资助金额:
    $ 1.8万
  • 项目类别:
c-Src/EGF Receptors Interactions and Therapeutic Resistance in Breast Cancer
乳腺癌中的 c-Src/EGF 受体相互作用和治疗耐药
  • 批准号:
    7826710
  • 财政年份:
    2006
  • 资助金额:
    $ 1.8万
  • 项目类别:
c-Src/EGF Receptors Interactions and Therapeutic Resistance in Breast Cancer
乳腺癌中的 c-Src/EGF 受体相互作用和治疗耐药
  • 批准号:
    7135324
  • 财政年份:
    2006
  • 资助金额:
    $ 1.8万
  • 项目类别:
Neuroendocrine cells in Prostate Cancer
前列腺癌中的神经内分泌细胞
  • 批准号:
    6868873
  • 财政年份:
    2004
  • 资助金额:
    $ 1.8万
  • 项目类别:
Neuroendocrine cells in Prostate Cancer
前列腺癌中的神经内分泌细胞
  • 批准号:
    6707695
  • 财政年份:
    2004
  • 资助金额:
    $ 1.8万
  • 项目类别:
c Src and EGF Receptor in Breast Cancer Development
c Src 和 EGF 受体在乳腺癌发展中的作用
  • 批准号:
    6690649
  • 财政年份:
    2003
  • 资助金额:
    $ 1.8万
  • 项目类别:
Neuroendocrine Cell Signaling in Prostate Cancer
前列腺癌中的神经内分泌细胞信号转导
  • 批准号:
    6563900
  • 财政年份:
    2002
  • 资助金额:
    $ 1.8万
  • 项目类别:

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ROLE OF CELL ADHESION IN BIOLOGICAL SIGNAL TRANSDUCTION
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  • 批准号:
    6238317
  • 财政年份:
    1997
  • 资助金额:
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  • 项目类别:
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    5210031
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