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J. Biol. Chem., Vol. 277, Issue 38, 35124-35132, September 20, 2002
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From the Ophioluxin, a potent platelet agonist, was
purified from the venom of Ophiophagus hannah (King cobra).
Under nonreducing conditions it has a mass of 85 kDa, similar to
convulxin, and on reduction gives two subunits with masses of 16 and 17 kDa, slightly larger than those of convulxin. The N-terminal sequences
of both subunits are very similar to those of convulxin and other
C-type lectins. Ophioluxin induces a pattern of tyrosine-phosphorylated
proteins in platelets like that caused by convulxin, when using
appropriate concentrations based on aggregation response, because it is
about 2-4 times more powerful as agonist than the latter. Ophioluxin and convulxin induce [Ca2+]i elevation both in
platelets and in Dami megakaryocytic cells, and each of these C-type
lectins desensitizes responses to the other. Convulxin agglutinates
fixed platelets at 2 µg/ml, whereas ophioluxin does not, even at 80 µg/ml. Ophioluxin resembles convulxin more than echicetin or
alboaggregin B because polyclonal anti-ophioluxin antibodies recognize
both ophioluxin and convulxin, but not echicetin, and platelets adhere
to and spread on ophioluxin- or convulxin-precoated surfaces in the
same way that is clearly different from their behavior on an
alboaggregin B surface. Immobilized ophioluxin was used to isolate the
glycoprotein VI-Fc
Ophioluxin, a Convulxin-like C-type Lectin from Ophiophagus
hannah (King Cobra) Is a Powerful Platelet Activator via
Glycoprotein VI*
,
,
,
¶
Theodor Kocher Institute, University of
Berne, CH-3012 Berne, Switzerland and § Serono
Pharmaceutical Research Institute, SA,
CH-1228 Geneva, Switzerland
complex from resting platelets, which also
contained Fyn, Lyn, Syk, LAT, and SLP76. Ophioluxin is the first
multiheterodimeric, convulxin-like snake C-type lectin, as well as the
first platelet agonist, to be described from the Elapidae snake family.
*
This work was supported by Grant 31-063868.00 (to K. J. C.) from the Swiss National Science Foundation.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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