The platelet collagen receptor glycoprotein VI is a member of the immunoglobulin superfamily closely related to Fc alpha R and the natural killer receptors
Jm. Clemetson et al., The platelet collagen receptor glycoprotein VI is a member of the immunoglobulin superfamily closely related to Fc alpha R and the natural killer receptors, J BIOL CHEM, 274(41), 1999, pp. 29019-29024
We have cloned the platelet collagen receptor glycoprotein (GP) VI from a h
uman bone marrow cDNA library using rapid amplification of cDNA ends with p
latelet mRNA to complete the 5' end sequence. GPVI was isolated from platel
ets using affinity chromatography on the snake C-type lectin, convulxin, as
a critical step. Internal peptide sequences were obtained, and degenerate
primers were designed to amplify a fragment of the GPVI cDNA, which was the
n used as a probe to screen the library. Purified GPVI, as well as Fab frag
ments of polyclonal antibodies made against the receptor, inhibited collage
n-induced platelet aggregation. The GPVI receptor cDNA has an open reading
frame of 1017 base pairs coding for a protein of 339 amino acids including
a putative 23-amino acid signal sequence and a 19-amino acid transmembrane
domain between residues 247 and 265, GPVI belongs to the immunoglobulin sup
erfamily, and its sequence is closely related to Fc alpha R and to the natu
ral killer receptors, Its extracellular chain has two Ig-C2-like domains fo
rmed by disulfide bridges. An arginine residue is found in position 3 of th
e transmembrane portion, which should permit association with Fc gamma and
its immunoreceptor tyrosine based activation motif via a salt bridge. With
51 amino acids, the cytoplasmic tail is relatively long and shows little ho
mology to the C-terminal part of the other family members. The ability of t
he cloned GPVI cDNA to code for a functional platelet collagen receptor was
demonstrated in the megakaryocytic cell line Dami, Dami cells transfected
with GPVI cDNA mobilized intracellular Ca2+ in response to collagen, unlike
the nontransfected or mock transfected Dami cells, which do not respond to
collagen.