Switch #: SWTI000625

Switch type: Binary

Switch subtype: Pre-translational

Description:
Alternative Splicing removes the degron motif of Prolactin receptor (PRLR) abrogating binding to F-box/WD repeat-containing protein 11 (FBXW11). SCF-beta-TrCP2 negatively regulates the long isoform of PRLR (Isoform 1 of Prolactin receptor (PRLR)). Should be noted that TrCP2 has a predominately cytoplasmic localisation compared to TrCP1 that is located in the nucleus. The mechanism for the down-regulation of the intermediate (Isoform Intermediate of Prolactin receptor (PRLR)) and short (Isoform Short form 1a of Prolactin receptor (PRLR) and Isoform Short form 1b of Prolactin receptor (PRLR)) that lack the TrCP degron is still not known. However it should be noted that the short and intermediate are either partially deficient or entirely deficient in mediating the signal transduction pathways induced by PRL (see Kine et al. (1999) (here) and Ross et al. (1997) (here)). This though is likely due to the missing STAT5-SH2-binding motif.

Participants:
(1) Prolactin receptor (PRLR)
(2) F-box/WD repeat-containing protein 11 (FBXW11)

(1) Negative regulation of prolactin receptor stability and signaling mediated by SCF(beta-TrCP) E3 ubiquitin ligase.
Li et al. Mol. Cell. Biol. (2004)