Essential role for Rap1 GTPase and its guanine exchange factor CalDAG-GEFI in LFA-1 but not VLA-4 integrin-mediated human T cell adhesion Running head: Rap1/CalDAG-GEFI in human T cell LFA-1 regulation
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Essential role for Rap1 GTPase and its guanine exchange factor CalDAG-GEFI in LFA-1 but not VLA-4 integrin mediated human T-cell adhesion.
Regulated adhesion of T cells by the integrins LFA-1 (lymphocyte function-associated antigen-1) and VLA-4 (very late antigen-4) is essential for T-cell trafficking. The small GTPase Rap1 is a critical activator of both integrins in murine lymphocytes and T-cell lines. Here we examined the contribution of the Rap1 regulatory pathway in integrin activation in primary CD3(+) human T cells. We demo...
متن کاملA LAD-III syndrome is associated with defective expression of the Rap-1 activator CalDAG-GEFI in lymphocytes, neutrophils, and platelets
Leukocyte and platelet integrins rapidly alter their affinity and adhesiveness in response to various activation (inside-out) signals. A rare leukocyte adhesion deficiency (LAD), LAD-III, is associated with severe defects in leukocyte and platelet integrin activation. We report two new LAD cases in which lymphocytes, neutrophils, and platelets share severe defects in beta(1), beta(2), and beta(...
متن کاملPLATELETS AND THROMBOPOIESIS CalDAG-GEFI is at the nexus of calcium-dependent platelet activation
The importance of the second messengers calcium (Ca2 ) and diacylglycerol (DAG) in platelet signal transduction was established more than 30 years ago. Whereas protein kinase C (PKC) family members were discovered as the targets of DAG, little is known about the molecular identity of the main Ca2 sensor(s). We here identify Ca2 and DAG-regulated guanine nucleotide exchange factor I (CalDAG-GEFI...
متن کاملCalDAG-GEFI is at the nexus of calcium-dependent platelet activation.
The importance of the second messengers calcium (Ca(2+)) and diacylglycerol (DAG) in platelet signal transduction was established more than 30 years ago. Whereas protein kinase C (PKC) family members were discovered as the targets of DAG, little is known about the molecular identity of the main Ca(2+) sensor(s). We here identify Ca(2+) and DAG-regulated guanine nucleotide exchange factor I (Cal...
متن کاملMice lacking the signaling molecule CalDAG-GEFI represent a model for leukocyte adhesion deficiency type III.
Single gene mutations in beta integrins can account for functional defects of individual cells of the hematopoietic system. In humans, mutations in beta(2) integrin lead to leukocyte adhesion deficiency (LAD) syndrome and mutations in beta(3) integrin cause the bleeding disorder Glanzmann thrombasthenia. However, multiple defects in blood cells involving various beta integrins (beta(1), beta(2)...
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تاریخ انتشار 2007