Dobashi K, Weiner D B, Greene M I
Department of Pathology, University of Pennsylvania, Philadelphia 19104-6082.
DNA. 1989 Dec;8(10):723-32. doi: 10.1089/dna.1989.8.723.
185c-neu is a member of a family of growth factor receptors with tyrosine kinase activity. A point mutation in the transmembrane region leads to activation of the enzymatic domain. We demonstrate that TPA (phorbol-12-myristate-13-acetate) stimulates the phosphorylation of p185c-neu on serine and threonine residues coincident with the inhibition of its intrinsic tyrosine kinase and the proliferation of cells that express it. The tyrosine kinase activity as well as the phosphorylation pattern of serine and threonine residues of oncogenic p185 (p185neu) and the growth of p185neu-expressing cells are not influenced by TPA. These observations indicate that the functional activity of p185c-neu can be regulated through protein kinase C (PKC) but the transmembrane point mutation present in p185neu renders it refractory to serine/threonine kinase regulation.
185c-neu是具有酪氨酸激酶活性的生长因子受体家族的一员。跨膜区域的一个点突变导致酶结构域的激活。我们证明，佛波醇-12-肉豆蔻酸酯-13-乙酸酯（TPA）刺激p185c-neu丝氨酸和苏氨酸残基的磷酸化，同时抑制其内在酪氨酸激酶以及表达它的细胞的增殖。致癌性p185（p185neu）的酪氨酸激酶活性以及丝氨酸和苏氨酸残基的磷酸化模式以及表达p185neu的细胞的生长不受TPA影响。这些观察结果表明，p185c-neu的功能活性可以通过蛋白激酶C（PKC）调节，但p185neu中存在的跨膜点突变使其对丝氨酸/苏氨酸激酶调节具有抗性。
