A new constitutively activating mutation of the Gs protein alpha subunit-gsp oncogene is found in human pituitary tumours.
A new constitutively activating mutation of the Gs protein alpha subunit-gsp oncogene is found in human pituitary tumours.
复制标题
在人类垂体肿瘤中发现了 Gs 蛋白 α 亚基 -gsp 癌基因的新组成型激活突变。
作者：
E. Clementi;N. Malgaretti;J. Meldolesi;R. Taramelli
一个新的227 Gln-Lys致癌突变的Gs α亚单位（GTP结合蛋白，刺激腺苷酸环化酶）已被发现在三个八人生长激素分泌垂体肿瘤的第2组，其特征是高cAMP和组成性激活腺苷酸环化酶。另外5个第2组肿瘤表达了另一个先前描述的突变，201 Arg-Cys，而第1组肿瘤的特征是正常的cAMP和腺苷酸环化酶活性，既不表达这些突变，也不表达先前在第2组中描述的相同位点的另外两个突变。α s的Gln 227位点对应于低分子量G蛋白p21 ras中的Gln 61位点，其中Leu取代已被证明是致癌的。到目前为止观察到的突变的致癌潜力（gsp癌基因）取决于α s固有的GT3活性降低，蛋白质的组成性激活和cAMP的显著升高。后者是刺激垂体生长激素分泌细胞和其他细胞类型生长的细胞内信使。
A new 227 Gln----Lys oncogenic mutation of the Gs alpha subunit (the GTP-binding protein that stimulates adenylyl cyclase) has been found in three out of eight human growth hormone-secreting pituitary tumours of the group 2, characterized by high cAMP and constitutively activated adenylyl cyclase. The additional five group 2 tumours expressed another, previously described mutation, 201 Arg----Cys, while the tumours of group 1, characterized by normal cAMP and adenylyl cyclase activity, expressed neither these nor the two other mutations of the same sites previously described in group 2. The Gln 227 site of alpha s corresponds to the Gln 61 site in the low Mw G protein, p21 ras, where the Leu substitution had already been shown to be oncogenic. The oncogenic potential (gsp oncogene) of the mutations so far observed depends on the reduced GTPase activity intrinsic to alpha s, with constitutive activation of the protein and marked elevation of cAMP. The latter is the intracellular messenger that stimulates growth of pituitary growth hormone-secreting cells and other cell types.