Roles of charged amino acid residues in the cytoplasmic domain of proHB-EGF

Biochemical and Biophysical Research Communications
Daisuke NanbaS Higashiyama

Abstract

Heparin-binding EGF-like growth factor (HB-EGF) is initially synthesized as a type I transmembrane precursor (proHB-EGF). Proteolytic cleavage of proHB-EGF yields amino- and carboxy-terminal fragments (HB-EGF and HB-EGF-C, respectively). We have previously shown that HB-EGF-C is translocated from the plasma membrane into the nucleus, where it interacts with the transcription repressor, PLZF. Here we characterize the amino acid residues of the cytoplasmic domain of proHB-EGF on cell surface distribution and the interaction of HB-EGF-C with PLZF. The cytoplasmic domain contains three characteristic clusters with charged amino acids. Generation of various mutants of proHB-EGF showed that the arrangement of the charged amino acids in the cytoplasmic domain regulates the distribution of proHB-EGF at the plasma membrane but does not regulate proHB-EGF processing and internalization of HB-EGF-C. Further, the charged amino acids are also required for HB-EGF-C-PLZF interaction. These results indicate that the cytoplasmic domain of proHB-EGF is a multifunctional domain.

References

Jan 1, 1993·Annual Review of Biochemistry·J Massagué, A Pandiella
Mar 7, 2003·Proceedings of the National Academy of Sciences of the United States of America·Ryo IwamotoEisuke Mekada
Jun 25, 2003·The Journal of Cell Biology·Jianxin BaoDavid A Talmage
Nov 5, 2003·The Journal of Cell Biology·Daisuke NanbaShigeki Higashiyama
Jan 30, 2004·Cytokine & Growth Factor Reviews·Daisuke Nanba, Shigeki Higashiyama

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