PMID- 7556068
OWN - NLM
STAT- MEDLINE
DCOM- 19951027
LR  - 20220511
IS  - 0261-4189 (Print)
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Linking)
VI  - 14
IP  - 17
DP  - 1995 Sep 1
TI  - Heregulin-dependent regulation of HER2/neu oncogenic signaling by 
      heterodimerization with HER3.
PG  - 4267-75
AB  - Amplification and/or overexpression of HER2/neu and HER3 genes have been 
      implicated in the development of cancer in humans. The fact that these receptor 
      tyrosine kinases (RTKs) are frequently coexpressed in tumor-derived cell lines 
      and that heterodimers form high affinity binding sites for heregulin (HRG) 
      suggests a novel mechanism for signal definition, diversification or 
      amplification. In cells expressing HER2 and HER3, tyrosine phosphorylation of 
      HER3 is markedly increased upon exposure to recombinant HRG. ATP binding site 
      mutants of HER2 and HER3 demonstrate transphosphorylation of HER3 by HER2, but 
      not vice versa. HRG-induced transphosphorylation of HER3 results in a substrate 
      phosphorylation pattern distinct from HER2 cells and enhances association of the 
      receptor with SHC and phosphoinositol 3-kinase in transfected 293 and mammary 
      carcinoma-derived MCF-7 cells. The physiological relevance of HER2/HER3 
      heterodimerization is demonstrated by HRG-dependent transformation of NIH 3T3 
      cells coexpressing the two receptors. These findings demonstrate the acquisition 
      of expanded signaling capacities for HER2 by HRG-induced heterodimerization with 
      HER3 and provide a molecular basis for the involvement of receptor 
      heteroactivation in the development of human malignancies.
FAU - Wallasch, C
AU  - Wallasch C
AD  - Department of Molecular Biology, Max-Planck-Institut fur Biochemie, Martinsried, 
      Germany.
FAU - Weiss, F U
AU  - Weiss FU
FAU - Niederfellner, G
AU  - Niederfellner G
FAU - Jallal, B
AU  - Jallal B
FAU - Issing, W
AU  - Issing W
FAU - Ullrich, A
AU  - Ullrich A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (DNA Primers)
RN  - 0 (Glycoproteins)
RN  - 0 (Macromolecular Substances)
RN  - 0 (Neuregulins)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 2.7.10.1 (Receptor, ErbB-3)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Base Sequence
MH  - Cell Line
MH  - DNA Primers
MH  - ErbB Receptors/biosynthesis/*metabolism/*physiology
MH  - *Gene Expression
MH  - Glycoproteins/*pharmacology
MH  - Humans
MH  - Macromolecular Substances
MH  - Melanoma
MH  - Mice
MH  - Molecular Sequence Data
MH  - Neuregulins
MH  - Oligonucleotides, Antisense
MH  - Phosphatidylinositol 3-Kinases
MH  - Phosphorylation
MH  - Phosphotransferases (Alcohol Group Acceptor)/metabolism
MH  - Polymerase Chain Reaction
MH  - Proto-Oncogene Proteins/biosynthesis/*metabolism/*physiology
MH  - Receptor Protein-Tyrosine Kinases/*metabolism
MH  - Receptor, ErbB-2/biosynthesis/*metabolism
MH  - Receptor, ErbB-3
MH  - Restriction Mapping
MH  - *Signal Transduction
MH  - Tumor Cells, Cultured
PMC - PMC394510
EDAT- 1995/09/01 00:00
MHDA- 1995/09/01 00:01
PMCR- 1996/09/01
CRDT- 1995/09/01 00:00
PHST- 1995/09/01 00:00 [pubmed]
PHST- 1995/09/01 00:01 [medline]
PHST- 1995/09/01 00:00 [entrez]
PHST- 1996/09/01 00:00 [pmc-release]
AID - 10.1002/j.1460-2075.1995.tb00101.x [doi]
PST - ppublish
SO  - EMBO J. 1995 Sep 1;14(17):4267-75. doi: 10.1002/j.1460-2075.1995.tb00101.x.