利索-全球专利检索

  1. 登录
  2. 注册

搜索结果

3 条记录 (耗时 0.05 秒)

    Methods to inhibit serine kinase activity and to alter intersubunit binding activity of phosphatidylinositol 3-kinase, and serine kinase active sequence of the same
    3.
    发明授权
    Methods to inhibit serine kinase activity and to alter intersubunit binding activity of phosphatidylinositol 3-kinase, and serine kinase active sequence of the same 失效
    抑制丝氨酸激酶活性和改变磷脂酰肌醇3-激酶的亚基间结合活性的方法和相同的丝氨酸激酶活性序列

    公开(公告)号：US5741689A

    公开(公告)日：1998-04-21

    申请号：US185424

    申请日：1994-01-21

    申请人： Ritu Bala Dhand ,  Michael Derek Waterfield ,  Ian Donald Hiles ,  Ivan Tarasovich Gout ,  Masato Kasuga ,  Kazuyoshi Yonezawa ,  Peter End ,  Michael Fry ,  George Panayotou

    发明人： Ritu Bala Dhand ,  Michael Derek Waterfield ,  Ian Donald Hiles ,  Ivan Tarasovich Gout ,  Masato Kasuga ,  Kazuyoshi Yonezawa ,  Peter End ,  Michael Fry ,  George Panayotou

    IPC分类号： A61K38/00 ,  C12N9/12

    CPC分类号： C12N9/1205 ,  A61K38/00 ,  C07K2319/00

    摘要： The invention provides for a method to inhibit the binding between the p85 and p110 subunits of said PI3-kinase and thus a method to modulate PI3-kinase activity and modulate the response of cells to external stimuli. In particular, disabling, by conventional means, residues located in the inter-SH2 domain of said p85 subunit, specifically a region containing amino acid residue 478 to amino acid residue 513 of p85.alpha. subunit, or amino acid residue 445 to amino acid residue 485 of p85.beta. subunit of said PI3-kinase. Interference with these binding regions will affect binding between the subunits and results in inhibiting PI3-kinase activity. This invention further relates to a methods to modulate the serine kinase activity of the PI3-kinase which can be achieved by disabling the DRHNSN sequence of the p110 subunit and can also be used to effect changes in overall PI3-kinase activity. This invention is further related to an (ant)agonist which affects serine kinase activity of PI3-kinase. An agonist is provided which stimulates the phosphorylation of the p85 subunit at the serine residue at position 608, wherein phosphorylation at the serine residue indirectly results in inhibiting PI3-kinase activity.

    摘要翻译： 本发明提供了抑制所述PI3激酶的p85和p110亚基之间的结合的方法，因此提供了调节PI3-激酶活性并调节细胞对外部刺激的反应的方法。 特别地，通过常规方法使位于所述p85亚基的SH2结构域之间的残基，特别是含有p85α亚基的氨基酸残基478至氨基酸残基513或氨基酸残基445至氨基酸残基485的区域 的所述PI3激酶的p85β亚基。 与这些结合区域的干扰将影响亚单位之间的结合并导致抑制PI3-激酶活性。 本发明还涉及调节PI3激酶的丝氨酸激酶活性的方法，其可以通过使p110亚单位的DRHNSN序列失活来实现，并且还可以用于影响整体PI3-激酶活性的变化。 本发明还涉及影响PI3激酶丝氨酸激酶活性的（蚂蚁）激动剂。 提供了激动剂，其刺激位置608的丝氨酸残基处的p85亚基的磷酸化，其中丝氨酸残基处的磷酸化间接导致抑制PI3-激酶活性。