Interaction of the PA2G4 (EBP1) protein with ErbB-3 and regulation of this binding by heregulin.
The processes by which ErbB-3, an inactive tyrosine kinase, exerts its biological effects are poorly understood. Using the yeast two-hybrid system, we have isolated an ErbB-3 binding protein (Ebp1) that interacts with the juxtamembrane domain of ErbB-3. This protein is identical to that predicted to be encoded for by the human PA2G4 gene. Ebp1 is the human homologue of a previously identified cell cycle-regulated mouse protein p38-2G4. Two transcripts of ebp1 mRNA (1.7 and 2.2 kb) were detected in several normal human organs. The interaction of Ebp1 with ErbB-3 was examined in vitro and in vivo. The first 15 amino acids of the juxtamembrane domain of ErbB-3 were essential for Ebp1 binding in vitro. Treatment of AU565 cells with the ErbB-3 ligand heregulin resulted in dissociation of Ebp1 from ErbB-3. Ebp1 translocated from the cytoplasm into the nucleus following heregulin stimulation. These findings suggest that Ebp1 may be a downstream member of an ErbB-3-regulated signal transduction pathway.
Yoo
J Y
JY
Molecular and Cellular Biology Program, University of Maryland, Baltimore 21201, USA.
Wang
X W
XW
Rishi
A K
AK
Lessor
T
T
Xia
X M
XM
Gustafson
T A
TA
Hamburger
A W
AW
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D001483:Base Sequence; D001692:Biological Transport; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D017931:DNA Primers; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D020890:Neuregulin-1 / Q000378:metabolism*; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000737:chemistry / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D000099160:LexA Repressor Protein
D001426:Bacterial Proteins; D017931:DNA Primers; D066246:ErbB Receptors; D020890:Neuregulin-1; D012333:RNA, Messenger; D020893:Receptor, ErbB-3; D012697:Serine Endopeptidases; D000099160:LexA Repressor Protein