Switch #: SWTI000290

Switch type: Specificity

Switch subtype: Altered binding specificity

Description:
Phosphorylation-dependent binding of Receptor tyrosine-protein kinase erbB-4 (ERBB4) to the SH2 domains of Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1) results in signaling activation, while binding to the WW domains of E3 ubiquitin-protein ligase Itchy homolog (ITCH) to unphopshorylated ERBB4 results in ubiquitylation, endocytosis and ultimately degradation of ERBB4.

Participants:
(1) Receptor tyrosine-protein kinase erbB-4 (ERBB4)
(2) E3 ubiquitin-protein ligase Itchy homolog (ITCH)
(3) Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1)

(1) Isoform-specific monoubiquitination, endocytosis, and degradation of alternatively spliced ErbB4 isoforms.
Sundvall et al. Proc. Natl. Acad. Sci. U.S.A. (2008)

(2) ErbB4 splice variants Cyt1 and Cyt2 differ by 16 amino acids and exert opposing effects on the mammary epithelium in vivo.
Muraoka-Cook et al. Mol. Cell. Biol. (2009)

(3) Cell death or survival promoted by alternative isoforms of ErbB4.
Sundvall et al. Mol. Biol. Cell (2010)

(4) HER4-mediated biological and biochemical properties in NIH 3T3 cells. Evidence for HER1-HER4 heterodimers.
Cohen et al. J. Biol. Chem. (1996)

Other switches involving participants
Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1) - 6 more (view)
Receptor tyrosine-protein kinase erbB-4 (ERBB4) - 4 more (view)
E3 ubiquitin-protein ligase Itchy homolog (ITCH) - 3 more (view)

Other switches involving interfaces
LIG_SH2_STAT5 - 7 more (view)
SH2 domain - 140 more (view)
WW domain - 105 more (view)
LIG_WW_1 - 17 more (view)