Reaction: PTPN13:PLEKHA1,2 bind PI(3,4)P2
- in pathway: Synthesis of PIPs at the plasma membrane
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).
Reaction - small molecule participants:
PI(3,4)P2 [plasma membrane]
Reactome.org reaction link: R-HSA-8870332
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Reaction input - small molecules:
1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
Reaction output - small molecules:
Reactome.org link: R-HSA-8870332