Kashiwagi H, Honda S, Tomiyama Y, Mizutani H, Take H, Honda Y, Kosugi S, Kanayama Y, Kurata Y, Matsuzawa Y
Second Department of Internal Medicine, Osaka University Medical School, Japan.
Thromb Haemost. 1993 May 3;69(5):481-4.
To clarify the molecular basis of the deficiency of glycoprotein IV (GPIV) of the platelet surface, we analyzed GPIV cDNA synthesized from platelet RNA of five unrelated Japanese subjects whose platelets did not express GPIV. We confirmed the presence of normal-sized GPIV mRNA in platelets from subjects with GPIV deficiency. The sequence of platelet GPIV cDNA from GPIV deficient subject showed three differences when compared with the published sequence; 1) a replacement of a 478CCT codon for proline-90 by TCT for serine, 2) a four-base insertion in the 3'-noncoding region, and 3) a substitution of A for 79C in the 5'-noncoding region. The replacement of Pro90 by Ser predominates in subjects with GPIV deficiency; that is, four out of five platelets with GPIV deficiency contained GPIV mRNA encoding GPIVSer-90, while all platelets from 17 GPIV positive subjects had GPIV mRNA encoding GPIVPro-90. The sequence of platelet GPIV cDNA which did not encode GPIVSer-90 from a subject with GPIV deficiency revealed no abnormality in the coding region. The four-base insertion in the 3'-noncoding region and the substitution of A for 79C in the 5'-noncoding region seems to be unrelated to the expression of GPIV. The substitution of Ser for Pro90 might alter the GPIV structure or impair GPIV biosynthesis, resulting in a lack of detectable GPIV. This hypothesis remains to be tested.
为阐明血小板表面糖蛋白IV（GPIV）缺乏的分子基础，我们分析了5名无亲缘关系的日本受试者血小板RNA合成的GPIV cDNA，这些受试者的血小板不表达GPIV。我们证实了GPIV缺乏受试者的血小板中存在正常大小的GPIV mRNA。与已发表序列相比，GPIV缺乏受试者的血小板GPIV cDNA序列显示出三个差异：1）脯氨酸-90的478CCT密码子被丝氨酸的TCT取代；2）3'-非编码区有一个四碱基插入；3）5'-非编码区79C被A取代。在GPIV缺乏的受试者中，脯氨酸90被丝氨酸取代占主导；也就是说，5名GPIV缺乏的受试者中有4名血小板含有编码GPIVSer-90的GPIV mRNA，而17名GPIV阳性受试者的所有血小板都有编码GPIVPro-90的GPIV mRNA。一名GPIV缺乏受试者中不编码GPIVSer-90的血小板GPIV cDNA序列在编码区未显示异常。3'-非编码区的四碱基插入和5'-非编码区79C被A取代似乎与GPIV的表达无关。脯氨酸90被丝氨酸取代可能会改变GPIV结构或损害GPIV生物合成，导致无法检测到GPIV。这一假设仍有待验证。
