RN181, a novel ubiquitin E3 ligase that interacts with the KVGFFKR motif of platelet integrin alpha(IIb)beta3.
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.
Brophy
Teresa M
TM
Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, 123 St. Stephens Green, Dublin 2, Ireland.
Raab
Markus
M
Daxecker
Heide
H
Culligan
Kevin G
KG
Lehmann
Ingo
I
Chubb
Anthony J
AJ
Treumann
Achim
A
Moran
Niamh
N
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001792:Blood Platelets / Q000201:enzymology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D017124:Conserved Sequence; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D012333:RNA, Messenger; C547603:RNF181 protein, human; D044767:Ubiquitin-Protein Ligases; D002118:Calcium