Glanzmann thrombasthenia resulting from a single amino acid substitution between the second and third calcium-binding domains of GPIIb. Role of the GPIIb amino terminus in integrin subunit association. J Clin Invest 1995 Apr;95(4):1553-60
Date
04/01/1995Pubmed ID
7706461Pubmed Central ID
PMC295643DOI
10.1172/JCI117828Scopus ID
2-s2.0-0028951764 (requires institutional sign-in at Scopus site) 66 CitationsAbstract
To gain insight into region of the platelet GPIIb-IIIa complex involved in receptor biogenesis and function, we examined the biochemical properties of a defective GPIIb-IIIa complex from patient suffering from type II Glanzmann thrombasthenia. Flow cytometric as well as immunoblot analysis of patient platelets showed significantly reduced levels of GPIIb and GPIIIa compared with a normal control. Patient platelets, however, retained the ability to retract a fibrin clot. Sequence analysis of PCR-amplified platelet GPIIb mRNA revealed an Arg327-->His amino acid substitution between the second and third calcium-binding domains of the GPIIb heavy chain, a residue that is highly conserved among integrin alpha-subunits. The recombinant His327 form of GPIIb was found to be fully capable of associating with GPIIIa, therefore the role of the calcium-binding domains in intersubunit association was further examined by constructing amino-terminal segments of GPIIb that ended before the first, second, and third calcium-binding domains. All three fragments were found to associate with GPIIIa, demonstrating that the calcium-binding domains of GPIIb are not necessary for initial complex formation. Regions amino-terminal to the calcium-binding domains of GPIIb may play a heretofore unappreciated role in integrin subunit association.
Author List
Wilcox DA, Paddock CM, Lyman S, Gill JC, Newman PJAuthor
David A. Wilcox PhD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentAmino Acid Sequence
Base Sequence
Blood Platelets
Calcium
Female
Fibrinogen
Flow Cytometry
Humans
Integrins
Molecular Sequence Data
Mutation
Platelet Membrane Glycoproteins
Protein Processing, Post-Translational
Structure-Activity Relationship
Thrombasthenia