PMID- 29632822
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240314
IS  - 2211-5463 (Print)
IS  - 2211-5463 (Electronic)
IS  - 2211-5463 (Linking)
VI  - 8
IP  - 4
DP  - 2018 Apr
TI  - ADAM17 is essential for ectodomain shedding of the EGF-receptor ligand 
      amphiregulin.
PG  - 702-710
LID - 10.1002/2211-5463.12407 [doi]
AB  - The epidermal growth factor (EGF)-receptor ligand amphiregulin (AREG) is a potent 
      growth factor implicated in proliferative skin diseases and in primary and 
      metastatic epithelial cancers. AREG, synthesized as a propeptide, requires 
      conversion to an active peptide by metalloproteases by a process known as 
      ectodomain shedding. Although (ADAM17) a disintegrin and metalloprotease 17 is a 
      key sheddase of AREG, ADAM8-, ADAM15-, and batimastat (broad metalloprotease 
      inhibitor)-sensitive metalloproteases have also been implicated in AREG shedding. 
      In the present study, using a curly bare (Rhbdf2(cub) ) mouse model that shows 
      loss-of-hair, enlarged sebaceous gland, and rapid cutaneous wound-healing 
      phenotypes mediated by enhanced Areg mRNA and protein levels, we sought to 
      identify the principal ectodomain sheddase of AREG. To this end, we generated 
      Rhbdf2(cub) mice lacking ADAM17 specifically in the skin and examined the above 
      phenotypes of Rhbdf2(cub) mice. We find that ADAM17 deficiency in the skin of 
      Rhbdf2(cub) mice restores a full hair coat, prevents sebaceous gland enlargement, 
      and impairs the rapid wound-healing phenotype observed in Rhbdf2(cub) mice. 
      Furthermore, in vitro, stimulated shedding of AREG is abolished in Rhbdf2(cub) 
      mouse embryonic keratinocytes lacking ADAM17. Thus, our data support previous 
      findings demonstrating that ADAM17 is the major ectodomain sheddase of AREG.
FAU - Hosur, Vishnu
AU  - Hosur V
AD  - The Jackson Laboratory Bar Harbor ME USA.
FAU - Farley, Michelle L
AU  - Farley ML
AD  - The Jackson Laboratory Bar Harbor ME USA.
FAU - Burzenski, Lisa M
AU  - Burzenski LM
AD  - The Jackson Laboratory Bar Harbor ME USA.
FAU - Shultz, Leonard D
AU  - Shultz LD
AD  - The Jackson Laboratory Bar Harbor ME USA.
FAU - Wiles, Michael V
AU  - Wiles MV
AD  - The Jackson Laboratory Bar Harbor ME USA.
LA  - eng
GR  - P30 CA034196/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20180312
PL  - England
TA  - FEBS Open Bio
JT  - FEBS open bio
JID - 101580716
PMC - PMC5881543
OTO - NOTNLM
OT  - ADAM17
OT  - EGFR
OT  - RHBDF2
OT  - amphiregulin
OT  - ectodomain shedding
OT  - epithelial cancer
EDAT- 2018/04/11 06:00
MHDA- 2018/04/11 06:01
PMCR- 2018/03/12
CRDT- 2018/04/11 06:00
PHST- 2017/11/15 00:00 [received]
PHST- 2018/02/09 00:00 [revised]
PHST- 2018/02/13 00:00 [accepted]
PHST- 2018/04/11 06:00 [entrez]
PHST- 2018/04/11 06:00 [pubmed]
PHST- 2018/04/11 06:01 [medline]
PHST- 2018/03/12 00:00 [pmc-release]
AID - FEB412407 [pii]
AID - 10.1002/2211-5463.12407 [doi]
PST - epublish
SO  - FEBS Open Bio. 2018 Mar 12;8(4):702-710. doi: 10.1002/2211-5463.12407. 
      eCollection 2018 Apr.