RN181, a novel ubiquitin E3 ligase that interacts with the KVGFFKR motif of platelet integrin αIIbβ3

• DOI: 10.1016/j.bbrc.2008.02.142
• Publication Date: 2008-03-11T13:29:06Z
• Authors: Teresa M. Brophy; Markus Raab; Heide Daxecker; Kevin G. Culligan; Ingo Lehmann; Anthony J. Chubb; Achim Treumann; Niamh Moran
• Keywords: Blood Platelets; Models, Molecular; 0301 basic medicine; Ubiquitin-Protein Ligases; Amino Acid Motifs; Molecular Sequence Data; Ubiquitination; Platelet Glycoprotein GPIIb-IIIa Complex; Protein Structure, Tertiary; 3. Good health; 03 medical and health sciences; Humans; Calcium; Amino Acid Sequence; RNA, Messenger; Conserved Sequence

We previously identified proteins that bind with high affinity to a peptide corresponding to the cytoplasmic regulatory domain (KVGFFKR) of the platelet-specific integrin subunit alpha(IIb). These included a hypothetical protein termed HSPC238, recently renamed as RING finger protein, RN181. Here, we establish the presence of RN181 in human platelets by RT-PCR, Western blotting and mass spectrometry and confirm its affinity for the platelet integrin. We demonstrate that RN181 has ubiquitin E3 ligase activity and that all other components of the ubiquitination pathway are abundant in platelets, suggesting a novel link of integrin signal transduction pathways with ubiquitin-conjugation events.