PTPN13:PLEKHA1,2 bind PI(3,4)P2

Insulin sensitivity is critically dependent on the activity of PI3K (phosphoinositide 3-kinase) and generation of the phosphatidylinositol 3,4, 5-triphosphate (PIP3,PtdIns(3,4,5)P(3)) second messenger. Increasing evidence suggests that one of the immediate breakdown products of PIP3, phosphatidylinositol 3,4-diphosphate (PIP2, PtdIns(3,4)P(2)), might also function as a signalling molecule by controlling a negative-feedback loop that down-regulates the insulin and PI3K network. The pleckstrin homology domain-containing family A members 1 and 2 (PLEKHA1 and PLEKHA2, aka TAPP1 and TAPP2 respectively) can both specifically bind PIP2. PLEKHA1 and 2 are constituitively bound to tyrosine-protein phosphatase non-receptor type 13 (PTPN13, aka PTPL1) via its first PDZ domain and this interaction keeps PLEKHA1 and 2 localised to the cytosol (Kimber et al. 2003). With increasing PIP2 levels, produced by PI3K activity on PIP3, PTPN13-bound PLEKHA1 and 2 translocate to the plasma membrane where they bind PIP2 (Marshall et al. 2002, Wullschleger et al. 2011).

胰岛素敏感性对PI3K（磷脂酰肌醇3激酶）的活性及其产生的磷脂酰肌醇3,4,5-三磷酸（PIP3，PtdIns(3,4,5)P(3)）第二信使的产生具有至关重要的依赖性。越来越多的证据表明，PIP3的即时分解产物之一，磷脂酰肌醇3,4-二磷酸（PIP2，PtdIns(3,4)P(2)），也可能通过调控胰岛素和PI3K网络的负反馈回路，作为一种信号分子发挥作用。Pleckstrin同源结构域家族A成员1和2（PLEKHA1和PLEKHA2，亦称TAPP1和TAPP2）均可特异性地结合PIP2。PLEKHA1和2通过其第一个PDZ结构域与酪氨酸蛋白磷酸酶非受体型13（PTPN13，亦称PTPL1）构成性结合，这种相互作用使得PLEKHA1和2定位于细胞质中（Kimber等人，2003年）。随着PI3K在PIP3上产生的PIP2水平的增加，PTPN13结合的PLEKHA1和2转位至质膜，在那里它们与PIP2结合（Marshall等人，2002年，Wullschleger等人，2011年）。