PMID- 14996914
OWN - NLM
STAT- MEDLINE
DCOM- 20041210
LR  - 20141120
IS  - 0021-9533 (Print)
IS  - 0021-9533 (Linking)
VI  - 117
IP  - Pt 8
DP  - 2004 Mar 15
TI  - Membrane-associated HB-EGF modulates HGF-induced cellular responses in MDCK 
      cells.
PG  - 1365-79
AB  - In MDCK cells, hepatocyte growth factor/scatter factor (HGF/SF) induces 
      epithelial cell dissociation, scattering, migration, growth and formation of 
      branched tubular structures. By contrast, these cells neither scatter nor form 
      tubular structures in response to the epidermal growth factor (EGF) family of 
      growth factors. Heparin-binding EGF-like growth factor (HB-EGF) is a member of 
      the EGF family of growth factors and is synthesized as a membrane-associated 
      precursor molecule (proHB-EGF). ProHB-EGF is proteolytically cleaved to release a 
      soluble ligand (sHB-EGF) that activates the EGF receptor. Although recent studies 
      suggest possible physiological functions, the role of proHB-EGF remains largely 
      undefined. Using MDCK cells stably expressing proHB-EGF, a noncleavable deletion 
      mutant of proHB-EGF or soluble HB-EGF, we show that epithelial cell functions 
      differ depending on the form of HB-EGF being expressed. Expression of 
      noncleavable membrane-anchored HB-EGF promoted cell-matrix and cell-cell 
      interactions and decreased cell migration, HGF/SF-induced cell scattering and 
      formation of tubular structures. By contrast, expression of soluble HB-EGF 
      induced increased cell migration, decreased cell-matrix and cell-cell 
      interactions and promoted the development of long unbranched tubular structures 
      in response to HGF/SF. These findings suggest that HB-EGF can not only modulate 
      HGF/SF-induced cellular responses in MDCK cells but also that membrane-bound 
      HB-EGF and soluble HB-EGF give rise to distinctly different effects on cell-cell 
      and cell-extracellular matrix interactions.
FAU - Singh, Amar B
AU  - Singh AB
AD  - Department of Medicine, Vanderbilt University, Nashville, TN 37232-4794, USA.
FAU - Tsukada, Toshiaki
AU  - Tsukada T
FAU - Zent, Roy
AU  - Zent R
FAU - Harris, Raymond C
AU  - Harris RC
LA  - eng
GR  - CA68485/CA/NCI NIH HHS/United States
GR  - DK20593/DK/NIDDK NIH HHS/United States
GR  - DK51265/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040302
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Heparin-binding EGF-like Growth Factor)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Protein Precursors)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Communication/drug effects
MH  - Cell Line
MH  - Cell Movement/drug effects
MH  - Chick Embryo
MH  - Collagen/metabolism
MH  - Dogs
MH  - Electric Impedance
MH  - Epidermal Growth Factor/*physiology
MH  - Epithelial Cells/*cytology/drug effects/*physiology
MH  - Gene Deletion
MH  - Heparin-binding EGF-like Growth Factor
MH  - Hepatocyte Growth Factor/*pharmacology/physiology
MH  - Intercellular Signaling Peptides and Proteins
MH  - Precipitin Tests
MH  - Protein Precursors/genetics/*metabolism
MH  - Solubility
EDAT- 2004/03/05 05:00
MHDA- 2004/12/16 09:00
CRDT- 2004/03/05 05:00
PHST- 2004/03/05 05:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/03/05 05:00 [entrez]
AID - jcs.01037 [pii]
AID - 10.1242/jcs.01037 [doi]
PST - ppublish
SO  - J Cell Sci. 2004 Mar 15;117(Pt 8):1365-79. doi: 10.1242/jcs.01037. Epub 2004 Mar 
      2.