SHB (SH2 domain-containing adapter protein B) functions as an adapter protein which regulates several signal transduction cascades by linking activated receptors to downstream signaling components []. It transmits signals from receptor tyrosine kinases regulating diverse processes such as apoptosis and differentiation []. It regulates normal oocyte and follicle development []and is required for appropriate hematopoietic and vascular differentiation in embryos [].
Frk (RAK) is a member of the Src non-receptor type tyrosine kinase family of proteins. The Frk subfamily is composed of Frk/Rak and Iyk/Bsk/Gst. It is expressed primarily epithelial cells. Frk is a nuclear protein and may function during G1 and S phase of the cell cycle and suppress growth []. Unlike the other Src members it lacks a glycine at position 2 of SH4 which is important for addition of a myristic acid moiety that is involved in targeting Src PTKs to cellular membranes []. FRK and SHB exert similar effects when overexpressed in rat phaeochromocytoma (PC12) and beta-cells, where both induce PC12 cell differentiation and beta-cell proliferation. Under conditions that cause beta-cell degeneration these proteins augment beta-cell apoptosis. The FRK-SHB responses involve FAK and insulin receptor substrates (IRS) -1 and -2 []. Frk has been demonstrated to interact with retinoblastoma protein []. Frk regulates PTEN protein stability by phosphorylating PTEN, which in turn prevents PTEN degradation []. Frk also plays a role in regulation of embryonal pancreatic beta cell formation [].The Src non-receptor type tyrosine kinase (SFK) family members have an unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail. The SH2 domain of SFKs is involved in kinase autoinhibition and T-cell receptor signaling. The binding SH2 domains to phosphotyrosine (pY) sites is critical for the autoinhibition and substrate recognition of the SFKs [].
