PI-3-kinase p85 alpha
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Function
- binds to activated (phosphorylated) tyrosine kinases, through its SH2 domain
- acts as an adapter, mediating association of the p110 catalytic unit to the plasma membrane
- necessary for the insulin-stimulated increase in glucose uptake & glycogen synthesis in insulin-sensitive tissues
- heterodimer of a p110 (catalytic) & a p85 (regulatory) subunits
- interacts with phosphorylated TOM1L1
- interacts phosphorylated LIME1 upon TCR &/or BCR activation
- interacts with SOCS7
- interacts with RUFY3 (putative)
- interacts with phosphorylated LAT, LAX1 & TRAT1 upon TCR activation
- interacts with CBLB
- interacts with HIV-1 Nef to activate the Nef associated p21-activated kinase (PAK); this interaction depends on the C-terminus of both proteins & leads to increased production of HIV
- interacts with HCV NS5A
- SH2 domains interact with the YTHM motif of phosphorylated INSR in vitro
- also interacts with Tyr-phosphorylated IGF1R in vitro
- interacts with CD28 & CD3Z upon T-cell activation
- interacts with IRS1 & phosphorylated IRS4
- polyubiquitinated in T-cells by CBLB; which does not promote proteasomal degradation but impairs association with CD28 & CD3Z upon T-cell activation
Structure
- SH3 domain mediates the binding to CBLB, & to HIV-1 Nef
- belongs to the PI3K p85 subunit family
- contains 1 Rho-GAP domain
- contains 2 SH2 domains
- contains 1 SH3 domain
Alternative splicing
named isoforms=4
Expression
- isoform 2 is expressed in skeletal muscle & brain > kidney & cardiac muscle
- isoform 2 & isoform 4 are present in skeletal muscle (at protein level)
Pathology
- defects in PIK3R1 are a cause of severe insulin resistance