Hradetzky D, Strebhardt K, Rübsamen-Waigmann H
Chemotherapeutisches Forschungsinstitut Georg-Speyer-Haus, Frankfurt, Germany.
Gene. 1992 Apr 15;113(2):275-80. doi: 10.1016/0378-1119(92)90407-g.
Protein tyrosine kinases (PTKs) are implicated in the control of cell growth by virtue of their frequent appearance as products of retroviral oncogenes, as intracellular signal transducers, and as growth factor receptors or components thereof. The knowledge of the structure and sequence of family genes encoding PTKs is still limited. To date, the complete genomic structure of human src family members is only available for the C-FGR gene (encoding p55 Fgr, PTK). Sequence analysis and characterization of the intron/exon organization of the human HCK gene, encoding a hemopoietic-specific cell PTK of the src-related family, revealed a length of over 16 kb for the seven 3'-exons. All intron/exon splice junctions agree with the GT/AG rule. In each case where a boundary occurs at a Gly codon, GGG or GGA, the triplet is split between the first and second nucleotide (nt). A total of eight complete and one partial Alu repeats were identified within the introns. The nt sequence of the genomic clones resolves existing discrepancies among two published sequences of HCK cDNAs. Human HCK, C-SRC (encoding p60 Src PTK), C-FGR and LCK (encoding p56 Lck, PTK) genes thus share very similar exon/intron structures for the conserved exons. These results provide additional evidence that the different PTKs of the src-like family most likely arose by duplication of an ancestral src-like gene.
蛋白质酪氨酸激酶(PTKs)由于其常作为逆转录病毒癌基因的产物、细胞内信号转导分子、生长因子受体或其组成成分而与细胞生长的调控有关。编码PTKs的家族基因的结构和序列知识仍然有限。迄今为止,人类src家族成员的完整基因组结构仅在C-FGR基因(编码p55 Fgr,PTK)中可用。对编码src相关家族的造血特异性细胞PTK的人类HCK基因的内含子/外显子组织进行序列分析和表征,发现七个3'-外显子的长度超过16 kb。所有内含子/外显子剪接接头均符合GT/AG规则。在边界出现在甘氨酸密码子GGG或GGA处的每种情况下,三联体在第一个和第二个核苷酸(nt)之间分开。在内含子中总共鉴定出八个完整和一个部分Alu重复序列。基因组克隆的nt序列解决了HCK cDNA的两个已发表序列之间现有的差异。因此,人类HCK、C-SRC(编码p60 Src PTK)、C-FGR和LCK(编码p56 Lck,PTK)基因在保守外显子方面具有非常相似的外显子/内含子结构。这些结果提供了额外的证据,表明src样家族的不同PTKs很可能是由一个祖先src样基因的复制产生的。