Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/9751
Title: Proteolytic cleavage of platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) is regulated by a calmodulin-binding motif.
Authors: Wong, Mae-Xhum;Harbour, Stacey N;Wee, Janet L;Lau, Lai-Man;Andrews, Robert K;Jackson, Denise E
Affiliation: Kronheimer Building, Austin Research Institute, Austin Hospital, Heidelberg, Vic., Australia.
Issue Date: 18-Jun-2004
Citation: Febs Letters; 568(1-3): 70-8
Abstract: Homophilic engagement of platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) induces 'outside-in' signal transduction that results in phosphorylation events and recruitment and activation of signalling molecules. The formation of signalling scaffolds with PECAM-1 are important signalling events that modulate platelet secretion, aggregation and platelet thrombus formation. In this study, we describe a novel interaction between PECAM-1 and cytosolic calmodulin (CaM) in platelets. Reciprocal co-immunoprecipitation studies revealed that cytosolic CaM is constitutively associated with PECAM-1 in resting, thrombin activated and aggregated human platelets. Our studies demonstrate that CaM directly interacts with a PECAM-1 peptide (594-604) C595A containing the sequences (594)KAFYLRKAKAK(604). This CaM:PECAM-1 interaction has a threefold higher affinity than CaM:GPVI interaction. It is potentiated by the addition of calcium ions, and dissociated by the CaM inhibitor, trifluoperazine. Treatment of platelets with CaM inhibitors triggers cleavage of PECAM-1 in a time- and dose-dependent manner. Furthermore, this membrane proximal portion of PECAM-1 is conserved across mammalian species and the helical representation of basic/hydrophobic residues reveals a charge distribution analogous to other CaM-binding motifs in other proteins. Taken together, these results suggest that this highly charged cluster of amino acids in the PECAM-1 cytoplasmic domain directly interacts with CaM and this novel interaction appears to regulate cleavage of PECAM-1.
Internal ID Number: 15196923
URI: http://ahro.austin.org.au/austinjspui/handle/1/9751
DOI: 10.1016/j.febslet.2004.04.094
URL: http://www.ncbi.nlm.nih.gov/pubmed/15196923
Type: Journal Article
Subjects: Amino Acid Motifs
Amino Acid Sequence
Antigens, CD31.chemistry.metabolism
Binding Sites
Blood Platelets.metabolism
Calmodulin.antagonists & inhibitors.metabolism
Enzyme-Linked Immunosorbent Assay
Humans
Hydrolysis
Molecular Sequence Data
Sequence Homology, Amino Acid
Appears in Collections:Journal articles

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