title: Identification and structure of activated-platelet protein-1, a protein with RNA-binding domain motifs that is expressed by activated platelets.
abstract: Beyond their critical role in thrombosis, platelets perform important functions in vascular remodeling, inflammation, and wound repair. Many of these functions are executed by molecules expressed by activated platelets. A novel molecule, activated-platelet protein-1 (APP-1), was identified by a monoclonal antibody against activated rabbit platelets. When platelets were stimulated by thrombin, A23187 or ADP, APP-I was expressed on the platelet surface. APP-1 was also detected in whole cell lysates of platelets, but not on the external surfaces of resting platelets. With maximal activation by thrombin, 15 900 +/- 2800 molecules APP-1 were expressed/platelet. A 2.3-kb cDNA fragment containing a partial coding sequence for APP-1 was isolated from a rabbit bone marrow library by expression cloning with the anti-APP-1 monoclonal antibody. When expressed as a recombinant fusion protein in bacteria, APP-1 bound specifically to poly(A)-Sepharose. The full-length cDNA coding for human APP-1, obtained by DNA hybridization techniques, showed 98.7% amino acid sequence identity with the rabbit protein. Northern analysis with human APP-1 identified a 3.7-kb mRNA transcript in megakaryocytic lines that express transcripts for platelet proteins. Human APP-1 has four ribonucleotide binding domains with ribonucleoprotein 1 and 2 motifs. By virtue of its ribonucleotide binding domains, APP-1 is structurally related to polyadenylate-binding protein, which regulates translation initiation and polyadenylate shortening, and to nucleolysin, a specific effector molecule found in the granules of cytotoxic T lymphocytes.
authors.affiliation: Cardiovascular Biology Laboratory, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Houng
authors.forename: L
authors.initials: L
authors.lastname: Maggini
authors.forename: C Y
authors.initials: CY
authors.lastname: Clement
authors.forename: G L
authors.initials: GL
authors.lastname: Reed
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001483:Base Sequence; D001792:Blood Platelets / Q000737:chemistry / Q000378:metabolism*; D001798:Blood Proteins / Q000235:genetics / Q000302:isolation & purification*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008533:Megakaryocytes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D008970:Molecular Weight; D015539:Platelet Activation; D039102:Poly(A)-Binding Proteins; D014176:Protein Biosynthesis; D016601:RNA-Binding Proteins / Q000097:blood* / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification*; D011817:Rabbits; D016415:Sequence Alignment
chemical_list: D000911:Antibodies, Monoclonal; D001798:Blood Proteins; C104581:PABPC4 protein, human; D039102:Poly(A)-Binding Proteins; D016601:RNA-Binding Proteins