Intranuclear translocation signaling of HB-EGF carboxy-terminal fragment and mucosal defense through cell proliferation and migration in digestive tracts.
Mucosal integrity in the digestive tracts is maintained by defense mechanisms which comprise mucin production, microcirculatory blood flow, intercellular junctions, cell growth and mucosal repair. These physiological features are known to be regulated by prostaglandins, nitric oxides, growth factors, and cytokines. Mucosal injury and inflammation occur when cytotoxic attacks overwhelm cellular capacity for defense or repair. Interleukin-8 (IL-8) promotes tumor cell proliferation in colon cancer cells after binding to its receptors, which are members of the G-protein-coupled receptor (GPCR) family. Stimulation of GPCR can induce shedding of epidermal growth factor (EGF) ligands via activation of A disintegrin and metalloprotease (ADAM), with subsequent transactivation of the EGF receptor (EGFR). In parallel with EGF signaling through EGFR activation, heparin-binding (HB)-EGF carboxy-terminal fragment (CTF) signaling is also involved in cell proliferation through nuclear export of promyelocytic leukemia zinc finger. IL-8 induces cell proliferation and migration by an ADAM-dependent intranuclear translocation pathway of HB-EGF-CTF. Here, we focus on the mechanisms of IL-8-induced HB-EGF-CTF signaling, which is involved in cytoprotection and cellular repair.
Tanida
Satoshi
S
Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Aichi 467-8601, Japan. stanida @ med.nagoya-cu.ac.jp
Kataoka
Hiromi
H
Mizoshita
Tsutomu
T
Shimura
Takaya
T
Kamiya
Takeshi
T
Joh
Takashi
T
D051722:ADAM Proteins / Q000378:metabolism; D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000254:growth & development / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D054730:Protein Interaction Domains and Motifs; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000378:metabolism; D012038:Regeneration; D015398:Signal Transduction
D016209:Interleukin-8; D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D051722:ADAM Proteins