| Project/Area Number |
13670139
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Pathological medical chemistry
|
|---|
| Research Institution | Ehime University (2002)
Osaka University (2001) |
|---|
Principal Investigator |
HIGASHIYAMA Shigeki Ehime University, Faculty of Medicine, Professor, 医学部, 教授 (60202272)
|
|---|
| Project Period (FY) |
2001 – 2002
|
| Project Status |
Completed (Fiscal Year 2002)
|
| Budget Amount *help |
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥2,900,000 (Direct Cost: ¥2,900,000)
|
|---|
| Keywords | HB-EGF / shedding / ADAM / wound healing / EGF family / SH3 protein / keratinocyte / metalloprotease / Shedding / Angiotensin II / IL-8 / SH3蛋白質 / EGFファミリー / PACSIN3 / Wound Healing / Metalloprotease |
|---|
| Research Abstract |
1) TPA-dependent HB-EGF shedding was completely abrogated in ADAM12-/- mouse-derived embryonic fibroblast, but not in ADAM9-/- mouse-derived embryonic fibroblast, suggesting that ADAM12 is a key enzyme in HB-EGF shedding.
2) In order to analyze the activation mechanism of ADAM12, we screened proteins to bind the cytoplasmic of ADAM12 using a yeast two-hybrid method, resulting in the identification of two kinds of SH3 domain-containing proteins, PACSIN3 and a novel one designated Eve-1. PACSIN3 consists of 416 amino acids and has three SH3 domains in the C-terminal region. Eve-1 has two spliced isoforms, Eve-1a and Eve-1b which consists 767 and 790 amino acids, respectively. Eve-1a and Eve-1b have four and five SH3 domains in the C-terminal region. Overexpression of PACSIN3 and Eve-1a suppressed additively TPA-HB-EGF shedding.
Based on these data, we speculated that HB-EGF shedding would be regulated multiply by ADAM members and SH3 domain containing proteins.
|
