In the first step, holo-retinol binding protein (holo-RBP; simply means RBP bound to retinol, i.e. the RBP-ROH complex) binds to the extracellular portion of STRA6.  This facilitates the release of retinol through the transporter.  ROH is then transferred to cellular retinol binding protein 1 (CRBP1), an intracellular acceptor of retinol that attaches to the CRBP Binding Loop (or CBL) on STRA6.  This transport of ROH, in turn, activates JAK2, thereby phosphorylating STRA6 at the Y643 (tyrosine) residue.  This phosphorylation enables the extension of the CBL further into the cell.  Holo-CRBP-I, leaves the CBL and is replaced by apo-CRBP-I (unbound).  Holo-CRBP-I will continue to the Endoplasmic Reticulum (ER) where lecithin retinol acyltransferase (LRAT) is bound. ROH is released to LRAT which will convert retinol into retinylesters. Following the release of holo-CRBP-I from intercellular STRA6, STAT5 is recruited to STRA6 phosphorylated Y643 region where it is then phosphorylated by JAK2.  This phosphorylation activates STAT5 which then makes its way to the nucleus to induce expression of target genes including suppressor of cytokine signaling 3 (SOCS3), a strong inhibitor of insulin signaling.