ARF PROTEINS IN CELLULAR REGULATION OF PHOSPHOLIPASE D
ARF PROTEINS IN CELLULAR REGULATION OF PHOSPHOLIPASE D
批准号:
2770290
负责人:
GUILLERMO G ROMERO
金额:
$8.53万
依托单位国家:
美国
项目类别:
财政年份:
1996
资助国家:
美国
项目状态:
已结题
起止时间:
1996-09-30 至 2001-08-31
中文摘要
描述(摘自申请人摘要)
英文摘要
DESCRIPTION (Taken from the applicant's Abstract)
The members of the ARF family of small GTP-binding proteins play important
roles in the regulation of membrane traffic and recently have been shown to
activate cellular phospholipase D, an important modulator of cell function
and proliferation that is controlled by various types of extracellular
signals. However, the effects of extracellular signals on the state of
activation of ARF proteins has not been studied. Thus, although the effects
of ARF on phospholipase D activation strongly suggest a signalling role for
these proteins, the regulation of their activity by extracellular signals
remains to be demonstrated. Very recent work in the Principal
Investigator's laboratory has shown that ARF activation can be stimulated by
extracellular signals. Using as a model cells that overexpress wild type
human insulin receptors, we have shown that the activation of purified
bovine ARF by plasma membranes is enhanced by insulin. Cells that
overexpress mutated receptors do not show this behavior. Likewise, the
isoprenoid Brefeldin A, an agent that disrupts intracellular membrane
traffic and whose effects are linked to the inhibition of ARF activation,
has been shown to block insulin-induced receptor internalization and
activation of phospholipase D. A detailed investigation of the possible
mechanisms by which insulin might induce ARF activation revealed that the
insulin receptor and ARF co-precipitate with immobilized insulin-agarose or
with specific anti-insulin receptor antibodies. This co-precipitation was
inhibited by guanine nucleotides in a manner reminiscent of the interactions
of heterotrimeric G proteins with their specific receptors. It is proposed
to continue these studies to determine the nature of the interactions of ARF
proteins with the insulin receptor signalling system. The proposed studies
will focus on the following aspects: a) characterization of the
interactions between ARF and the insulin receptor using in vitro ARF
activation and binding reconstitution assays recently developed in this
laboratory; b) analysis of the interactions between the receptor and ARF
using a yeast two-hybrid system; c) development of a reconstitution assay to
study ARF activation by growth factors in vitro; d) development of a
cell-free reconstitution assay to study the role of ARF proteins in insulin-
and growth factor-mediated activation of phospholipase D; and e) test the
role of ARF proteins in receptor-mediated PLD activation using dominant
activated and negative ARF mutants in vitro and in cells that express the
mutated ARF protein.
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专著(0)
科研奖励(0)
会议论文
Parathyroid Hormone Receptor Type 1: Dynamics, Traffic and Recycling
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批准号:8002407
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项目类别:
-
资助金额:$22.73万
-
财政年份:2010
-
负责人:GUILLERMO G ROMERO
-
依托单位:
ROLE OF PHOSPHATIDIC ACID IN GROWTH FACTOR SIGNALING
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批准号:6517526
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项目类别:
-
资助金额:$22.43万
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财政年份:2000
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负责人:GUILLERMO G ROMERO
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依托单位:
ROLE OF PHOSPHATIDIC ACID IN GROWTH FACTOR SIGNALING
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批准号:6635124
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项目类别:
-
资助金额:$22.43万
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财政年份:2000
-
负责人:GUILLERMO G ROMERO
-
依托单位:
ROLE OF PHOSPHATIDIC ACID IN GROWTH FACTOR SIGNALING
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批准号:6381367
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项目类别:
-
资助金额:$22.46万
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财政年份:2000
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负责人:GUILLERMO G ROMERO
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依托单位:
ROLE OF PHOSPHATIDIC ACID IN GROWTH FACTOR SIGNALING
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批准号:6096891
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项目类别:
-
资助金额:$22.5万
-
财政年份:2000
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负责人:GUILLERMO G ROMERO
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依托单位:
ARF PROTEINS IN INSULIN SIGNALLING
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批准号:2713434
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项目类别:
-
资助金额:$10.43万
-
财政年份:1996
-
负责人:GUILLERMO G ROMERO
-
依托单位:
ARF PROTEINS IN CELLULAR REGULATION OF PHOSPHOLIPASE D
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批准号:2015657
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项目类别:
-
资助金额:$6.45万
-
财政年份:1996
-
负责人:GUILLERMO G ROMERO
-
依托单位:
ARF PROTEIN IN INSULIN SIGNALING
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批准号:6177518
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项目类别:
-
资助金额:$13.95万
-
财政年份:1996
-
负责人:GUILLERMO G ROMERO
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依托单位:
ARF PROTEIN IN INSULIN SIGNALING
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批准号:6517393
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项目类别:
-
资助金额:$19.91万
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财政年份:1996
-
负责人:GUILLERMO G ROMERO
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依托单位:
ARF PROTEINS IN INSULIN SIGNALLING
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批准号:2430263
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项目类别:
-
资助金额:$10.06万
-
财政年份:1996
-
负责人:GUILLERMO G ROMERO
-
依托单位:
ARF PROTEIN IN INSULIN SIGNALING
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批准号:2840961
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项目类别:
-
资助金额:$18.58万
-
财政年份:1996
-
负责人:GUILLERMO G ROMERO
-
依托单位:
ARF PROTEINS IN CELLULAR REGULATION OF PHOSPHOLIPASE D
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批准号:6176176
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项目类别:
-
资助金额:$9.83万
-
财政年份:1996
-
负责人:GUILLERMO G ROMERO
-
依托单位:
ARF PROTEINS IN CELLULAR REGULATION OF PHOSPHOLIPASE D
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批准号:2904966
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项目类别:
-
资助金额:$9.84万
-
财政年份:1996
-
负责人:GUILLERMO G ROMERO
-
依托单位:
ARF PROTEINS IN CELLULAR REGULATION OF PHOSPHOLIPASE D
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批准号:2518178
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项目类别:
-
资助金额:$6.45万
-
财政年份:1996
-
负责人:GUILLERMO G ROMERO
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依托单位:
ARF PROTEINS IN INSULIN SIGNALING
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批准号:2632812
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项目类别:
-
资助金额:$0.49万
-
财政年份:1996
-
负责人:GUILLERMO G ROMERO
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依托单位:
ARF PROTEIN IN INSULIN SIGNALING
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批准号:6381272
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项目类别:
-
资助金额:$18.13万
-
财政年份:1996
-
负责人:GUILLERMO G ROMERO
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依托单位:
ARF PROTEINS IN INSULIN SIGNALLING
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批准号:2152289
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项目类别:
-
资助金额:$14.89万
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财政年份:1996
-
负责人:GUILLERMO G ROMERO
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依托单位:
STUDIES ON THE GENERATION OF INSULIN MEDIATORS
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批准号:3463654
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项目类别:
-
资助金额:$9.6万
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财政年份:1989
-
负责人:GUILLERMO G ROMERO
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依托单位:
STUDIES ON THE GENERATION OF INSULIN MEDIATORS
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批准号:3463650
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项目类别:
-
资助金额:$9.41万
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财政年份:1989
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负责人:GUILLERMO G ROMERO
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依托单位:
GENERATION OF INSULIN MEDIATORS
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批准号:3463652
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项目类别:
-
资助金额:$10.16万
-
财政年份:1989
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负责人:GUILLERMO G ROMERO
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依托单位:
海外基金