GENETIC VAR OF HERPESVIRUS SAIMIRI TRANSFORMING PROTEIN & ASSOC W/ CELLULAR SRC

6株A亚群分离株的STP基因显示广泛的序列 变种。亚组A的STP被显示为与细胞源关联 并作为src激酶的体外底物。萨伊里疱疹病毒 A亚群的11号菌株含有一种名为saimiri的基因 转化相关蛋白，STP，它不是必需的 病毒复制，但对于体外永生和 该病毒的诱发淋巴瘤的能力。评估……的影响 6个A亚群STP功能和STP基因的序列变异 对分离的菌株进行克隆和测序。序列比对显示 在中心区内广泛的氨基酸替代，但 酸性氨基末端和疏水羧基末端良好 保守的。氨基酸同源性从73%到99%不等。 双向比较。氨基酸高度保守的YAEV/I基序 第115至118个残基之前是带负电荷的谷氨酸 残基，因此很好地匹配了结合的共识序列 到src家族激酶的SH2结构域。这些亚组A的STP 研究表明，菌株与细胞src有关，并且是一种内源基因。 Src激酶的体外底物。STP-A11基因突变分析显示 与src激酶的结合需要115个酪氨酸残基， 表明YAEV/I可能是src的结合基序。还有，酪氨酸 Src对STP-A11的磷酸化导致随后与Ick和Ick结合 Fyn在试管中。因此，stp与src的关联可能是 A亚群猪瘟病毒对T细胞转化的重要作用 疱疹病毒三文鱼。

STP genes from six subgroup A isolates show extensive sequence variation. STP of subgroup A is shown to associate with cellular src and to be an in vitro substrate for src kinase. Herpesvirus saimiri strain 11 of subgroup A contains a gene called the saimiri transformation-associated protein, STP, which is not required for viral replication but is required for in vitro immortalization and for the lymphoma-inducing capacity of the virus. To assess the effects of sequence variation on STP function, STP genes from six subgroup A isolates were cloned and sequenced. Sequence comparisons revealed extensive amino acid substitutions within the central region, but the acidic amino terminus and the hydrophobic carboxyl terminus were well conserved. Amino acid identities varied from 73 to 99% among all two-way comparisons. The highly conserved YAEV/I motif at amino acid residues 115 to 118 was preceded by negatively charged glutamic acid residues and thus matched very well the consensus sequence for binding to SH2 domains of src family kinases. The STPs of these subgroup A strains were shown to associate with cellular src and to be an in vitro substrate for src kinase. Mutational analysis of STP-A11 showed that binding to src kinase required the tyrosine residue at 115, showing that YAEV/I is a likely binding motif for src. Also, tyrosine phosphorylation of STP-A11 by src led to subsequent binding to Ick and fyn in vitro. Thus, the association of STP with src is likely to be important for T-cell transformation by subgroup A strains of herpesvirus saimiri.