NDLI: The small GTPase Rap1b regulates the cross talk between platelet integrin α2β1 and integrin αIIbβ3

Content Provider	PubMed Central
Author	Bernardi, Bruno Guidetti, Gianni F. Campus, Francesca Crittenden, Jill R. Graybiel, Ann M. Cesare, Balduini Torti, Mauro
Copyright Year	2006
Abstract	The involvement of the small GTPase Rap1b in platelet integrin α2β1-dependent outside-in signaling was investigated. Platelet adhesion to 4 different specific ligands for integrin α2β1, monomeric collagen, decorin, and collagen-derived peptides CB8(II) and CB11(II), induced a robust and rapid activation of Rap1b. This process did not require secreted ADP or thromboxane A2 production but was critically regulated by phospholipase C (PLC)–derived second messengers. Both Ca2+ and protein kinase C were found to organize independent but additive pathways for Rap1b activation downstream of integrin-α2β1, which were completely blocked by inhibition of PLC with U73122. Moreover, integrin α2β1 engagement failed to trigger Rap1b activation in murine platelets lacking CalDAG-GEFI, a guanine nucleotide exchange factor regulated by Ca2+ and diacylglycerol, despite normal phosphorylation and activation of PLCγ2. In addition, CalDAG-GEFI–deficient platelets showed defective integrin α2β1-dependent adhesion and spreading. We found that outside-in signaling through integrin α2β1 triggered inside-out activation of integrin αIIbβ3 and promoted fibrinogen binding. Similarly to Rap1b stimulation, this process occurred downstream of PLC activation and was dramatically impaired in murine platelets lacking the Rap1 exchange factor CalDAG-GEFI. These results demonstrate that Rap1b is an important element in integrin-dependent outside-in signaling during platelet adhesion and regulates the cross talk between adhesive receptors.
Related Links	http://dx.doi.org/10.1182/blood-2005-07-3023
Ending Page	2735
Page Count	8
Starting Page	2728
File Format	PDF
ISSN	00064971
e-ISSN	15280020
Journal	Blood
Issue Number	7
Volume Number	107
Language	English
Publisher	The American Society of Hematology
Publisher Date	2006-04-01
Access Restriction	Open
Rights Holder	The American Society of Hematology
Subject Keyword	Immunology Cell Biology Biochemistry Hematology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Hematology Biochemistry Immunology

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