BIOLOGY OF THE CELL ADHESION MOLECULE CD31
细胞粘附分子 CD31 的生物学
基本信息
- 批准号:3087822
- 负责人:
- 金额:$ 9.12万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1992
- 资助国家:美国
- 起止时间:1992-07-01 至 1995-06-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
CD31 is a recently described trans-membrane protein which belongs to the
immunoglobulin gene family of cell surface adhesion molecules. CD31
expression is restricted to vascular endothelium, leukocytes and platelets.
In vascular endothelial cells, CD31 is localized to intercellular
junctions. We have obtained several lines of data to suggest that CD31 may
play a role in the acute inflammatory response of endothelium and in
initial adhesion interactions occurring in the immune response: 1.
Stimulation of platelets or endothelial ells with acute inflammatory
agonists such as thrombin of histamine or T cell activation with
phytohemagglutinin results in immediate phosphorylation of CD31 by a
protein kinase C-dependent mechanism. 2. After T lymphocyte activation,
CD31 expression is down-regulated. 3. A CD31 monoclonal antibody, LYP21,
inhibits T lymphocyte activation in the allogeneic mixed lymphocyte
reaction. The goals of this project build upon our earlier work with CD31.
Aim #1: Characterization and functional consequences of CD31
phosphorylation. The stoichiometry of CD31 phosphorylation after cell
activation will be determined. The CD31 amino acids which are
phosphorylated with cell activation will be determined by incorporation of
radiolabeled phosphate during platelet activation, followed by acid
hydrolysis and amino acid chromatography. The functional consequences of
CD31 phosphorylation will be determined by utilizing a homotypic adhesion
model. CD31 protein will be purified and coated onto plastic in
phosphorylated and unphosphorylated forms. COS cells transfected with CD31
cDNA will be tested for binding to purified CD31 under resting and PKC-
activated conditions to determine: a) whether CD31 binding is homotypic or
heterotypic and b) the effects of phosphorylation upon CD31 binding
affinity.
Aim #2: Determination of CD31 adhesion domains. The CD31 monoclonal
antibody LYP21 interferes with the allogeneic mixed lymphocyte reaction,
suggesting that this epitope may be a functionally important domain on the
CD31 molecule. Based on our cloning data, we have tentatively localized
the probable LYP21 domain to a 23 amino acid region of the molecule. The
localization of adhesion epitopes of the related molecule ICAM-1 to the two
most distal domains makes it logical that CD31 adhesive function is also at
least in part mediated by epitopes in domains 1 and 2. Synthetic CD31
peptides based on the LYP21 epitope and sequences from the first and second
domains predicted to be hydrophilic, exposed and available for binding
interactions will be synthesized and tested for effects on CD31 binding.
Aim #3: Biological function of CD31. Knowledge and reagents gained from
the above aims will be used in two model systems to test the biological
function of CD31. Endothelial permeability, endothelial-leukocyte adhesion
and leukocyte trans-migration will be studied using cultured EC grown in a
two chamber system separated by a porous membrane. The role of CD31 in T
cell adhesion will be studied using the allogeneic mixed lymphocyte
reaction. It is likely that other function roles of CD31 will become
apparent as more is learned about this molecule. The detailed elucidation
of the biology of CD31, in terms of its structure-function relationship and
regulation of expression may shed important insights in our understanding
of the molecular events which occur in the initial stages of T cell
activation and the host response to acute inflammatory stimuli. Beyond the
inherent scientific interest of studying such cellular adhesion phenomena,
a more detailed understanding of these fundamental processes has the
potential for addressing problems of great clinical importance, including
the therapy of viral diseases, acute and chronic inflammatory diseases,
dissection of adhesion phenomena required for generation of the immune
response and hematogenous metastasis of malignant cells.
CD31是最近发现的一种跨膜蛋白
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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JAMES Lewis ZEHNDER其他文献
JAMES Lewis ZEHNDER的其他文献
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{{ truncateString('JAMES Lewis ZEHNDER', 18)}}的其他基金
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