Cloning and characterization of Xenopus laevis insulin receptor substrate (xIRS-u) and progesterone receptor (xPR).

Abstract

Xenopus laevis oocytes are physiologically arrested at G2 of meiosis I. Resumption of meiosis, or oocyte maturation, is triggered in vivo by progesterone, and in vitro by many hormones, such as insulin. Downstream of IGF-1 receptor activation is the activity of docking proteins such as xIRS-1 and xIRS-u. Sequence analysis suggested that xIRS-u was a novel member of the IRS family rather than a Xenopus homolog of an existing member. The cloned xIRS-u cDNA contains an amino-terminal pleckstrin homology (PH) domain and phosphotyrosine-binding (PTB) domain. The carboxy terminus of xIRS-u contains several potential Src homology 2 (SH2)-binding sites, five such sites are potential binding sites for phosphatidylinositol 3-kinase (YM/LXM). It also contains a putative binding site for Grb2 (YINID). The injection of xIRS-u mRNA accelerated insulin-induced MAP kinase activation and oocyte maturation. An amino-terminal deletion of the PH domain reduced the ability of xIRS-u to potentiate insulin signaling. (Abstract shortened by UMI.)