Characterization of a naturally occurring ErbB4 isoform that does not bind or activate phosphatidyl inositol 3-kinase.

摘要: Receptor tyrosine kinases regulate cell behavior by activating specific signal transduction cascades. Epidermal growth factor (EGF) receptor include ErbB1, ErbB2, ErbB3 and ErbB4. ErbB4 is a kinase that binds neuregulins (NRG) several other EGF family members. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis identified two isoforms of differed in their cytoplasmic domain sequences. Specifically, RT-PCR using primers flanking the putative phosphatidyl inositol 3-kinase (PI3-K) binding site generated bands when human mouse heart kidney tissues were analysed. Cloning sequencing these products revealed one (ErbB4 CYT-2) lacked 16 amino acid sequence including PI3-K site, was present isoform CYT-1). suggested expression CYT-1 CYT-2 tissue-specific. Heart, breast abdominal aorta expressed predominantly whereas neural CYT-2. To ascertain whether absence also resulted loss activity, NIH3T3 lines overexpressing or produced. NRG-1 bound to stimulated equivalent phosphorylation both isoforms. However, unlike CYT-1, unable bind p85 subunit stimulate activity cells. Furthermore, association with phosphotyrosine not induced treated cells expressing CYT-2, indicating this incapable even indirectly. It concluded novel naturally occurring exists deletion required for activation intracellular pathway only