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

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

Stable Identifier

R-HSA-8870332

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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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).

Literature References

PubMed ID	Title	Journal	Year
12101241	TAPP1 and TAPP2 are targets of phosphatidylinositol 3-kinase signaling in B cells: sustained plasma membrane recruitment triggered by the B-cell antigen receptor Marshall, AJ, Duronio, V, Krahn, AK, Ma, K, Hou, S	Mol. Cell. Biol.	2002
21204784	Role of TAPP1 and TAPP2 adaptor binding to PtdIns(3,4)P2 in regulating insulin sensitivity defined by knock-in analysis Wullschleger, S, Sakamoto, K, Alessi, DR, Gray, A, Wasserman, DH	Biochem. J.	2011
14516276	Interaction of the protein tyrosine phosphatase PTPL1 with the PtdIns(3,4)P2-binding adaptor protein TAPP1 Prescott, AR, Alessi, DR, Kimber, WA, Deak, M	Biochem. J.	2003