Novel alternatively spliced form of beta(3)-endonexin.
beta(3)-Endonexin is a binding protein to the cytoplasmic tail of beta(3) integrin and can activate alpha(IIb)beta(3) in Chinese hamster ovary (CHO) cells. Initially, two forms were identified, and only the shorter form showed the function. However, it localized mainly to the nucleus because of a nuclear localization signal (K(62)RKK). We identified two additional forms of beta(3)-endonexin. One encoded 177 amino acids and was identical to the protein previously reported as a thyroid hormone receptor-binding protein. The other is a novel shortest form encoding 62 amino acids. Although the novel form lacked nuclear localization signal and was observed diffusely in the cytoplasm of transfected cells, this form did not show interaction with beta(3) integrin. Then, the ideal form as an integrin modulator was not found among these isoforms. Nevertheless, when the nuclear localization signal of the shorter form was disrupted, beta(3)-endonexin was localized near the cell surface and modulated the affinity of alpha(IIb)beta(3) more intensively. These results suggest the presence of various isoforms and the relationship between subcellular localization and integrin-activating function of beta(3)-endonexin.
Fujimoto
Tetsuro-Takahiro
TT
Department of Clinical Pharmaceutical Sciences, Graduate School of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. fujimot@hiroshima-u.ac.jp
Katsutani
Shinya
S
Shimomura
Takeshi
T
Fujimura
Kingo
K
D017398:Alternative Splicing; D019943:Amino Acid Substitution; D001773:Blood Cells / Q000737:chemistry; D002451:Cell Compartmentation; D006801:Humans; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D011506:Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000737:chemistry
C403295:ITGB3BP protein, human; D009687:Nuclear Proteins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D020033:Protein Isoforms; D011506:Proteins