FERMT2 explained

Fermitin family homolog 2 (FERMT2) also known as pleckstrin homology domain-containing family C member 1 (PLEKHC1) or kindlin-2 is a protein that in humans is encoded by the FERMT2 gene.^{[1] [2] [3]}

Kindlin-2 is the first of the kindlin protein to be discovered in 1994. It was detected in a screen for epidermal growth factor (EGF)-induced mRNAs and initially named mitogen-inducible gene 2 (Mig-2) protein.^[1]

Function

FERMT2 is a component of extracellular matrix structures in mammalian cells and is required for proper control of cell shape change.^[4]

A major task of kindlins is to regulate the activation of integrins.^[5]

Interactions

FERMT2 has been shown to interact with FBLIM1.

Role in health and diseases

• Loss of kindlin-2 in mice leads to peri-implantation lethality.^[6]
• Kindlin-2 is highly expressed in activated myofibroblasts for regulation of focal adhesion formation.^[7]
• Deletion of Kindlin-2 retards insulin secretion and reduces β-cell mass in mice.^[8]
• Elevated kindlin-2 expression was observed in tubular intestinal fibrosis of the kidney, a condition is characterized by massive expansion of the cortical interstitium, conversion of fibroblasts into myofibroblasts and progressive EMT of tubular epithelial cells.^[9]
• Kindlin-2 is required for angiogenesis and blood vessel homeostasis.^[10]
• Kindlin-2 can exert tumor-promoting or tumor-inhibiting functions based on tumor-type-dependent.^[11]
• FERMT2 modulates the Alzheimer's Disease risk by regulating APP metabolism and Aβ peptide production.^[12]

Further reading

• Kato K, Shiozawa T, Mitsushita J, Toda A, Horiuchi A, Nikaido T, Fujii S, Konishi I . Expression of the mitogen-inducible gene-2 (mig-2) is elevated in human uterine leiomyomas but not in leiomyosarcomas . Human Pathology . 35 . 1 . 55–60 . January 2004 . 14745725 . 10.1016/j.humpath.2003.08.019 .
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M . Global, in vivo, and site-specific phosphorylation dynamics in signaling networks . Cell . 127 . 3 . 635–48 . November 2006 . 17081983 . 10.1016/j.cell.2006.09.026 . free .
• Wang L, Deng W, Shi T, Ma D . URP2SF, a FERM and PH domain containing protein, regulates NF-kappaB and apoptosis . Biochemical and Biophysical Research Communications . 368 . 4 . 899–906 . April 2008 . 18280249 . 10.1016/j.bbrc.2008.02.024 .

External links

• FERMT2 Info with links in the Cell Migration Gateway

Notes and References

1. Wick M, Bürger C, Brüsselbach S, Lucibello FC, Müller R . Identification of serum-inducible genes: different patterns of gene regulation during G0-->S and G1-->S progression . Journal of Cell Science . 107 (Pt 1) . 1 . 227–39 . January 1994 . 10.1242/jcs.107.1.227 . 8175911 .
2. Weinstein EJ, Bourner M, Head R, Zakeri H, Bauer C, Mazzarella R . URP1: a member of a novel family of PH and FERM domain-containing membrane-associated proteins is significantly over-expressed in lung and colon carcinomas . Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease . 1637 . 3 . 207–16 . April 2003 . 12697302 . 10.1016/S0925-4439(03)00035-8 .
3. Web site: Entrez Gene: FERMT2 .
4. Tu Y, Wu S, Shi X, Chen K, Wu C . Migfilin and Mig-2 link focal adhesions to filamin and the actin cytoskeleton and function in cell shape modulation . Cell . 113 . 1 . 37–47 . April 2003 . 12679033 . 10.1016/S0092-8674(03)00163-6 . free .
5. Rognoni E, Ruppert R, Fässler R . The kindlin family: functions, signaling properties and implications for human disease . Journal of Cell Science . 129 . 1 . 17–27 . January 2016 . 26729028 . 10.1242/jcs.161190 . free .
6. Montanez E, Ussar S, Schifferer M, Bösl M, Zent R, Moser M, Fässler R . Kindlin-2 controls bidirectional signaling of integrins . Genes & Development . 22 . 10 . 1325–30 . May 2008 . 18483218 . 2377186 . 10.1101/gad.469408 .
7. He Y, Esser P, Schacht V, Bruckner-Tuderman L, Has C . Role of kindlin-2 in fibroblast functions: implications for wound healing . The Journal of Investigative Dermatology . 131 . 1 . 245–56 . January 2011 . 20861856 . 10.1038/jid.2010.273 . free .
8. Zhu K, Lai Y, Cao H, Bai X, Liu C, Yan Q, Ma L, Chen D, Kanaporis G, Wang J, Li L, Cheng T, Wang Y, Wu C, Xiao G . 6 . Kindlin-2 modulates MafA and β-catenin expression to regulate β-cell function and mass in mice . Nature Communications . 11 . 1 . 484 . January 2020 . 31980627 . 10.1038/s41467-019-14186-y . 6981167 . 2020NatCo..11..484Z . free .
9. Bielesz B, Sirin Y, Si H, Niranjan T, Gruenwald A, Ahn S, Kato H, Pullman J, Gessler M, Haase VH, Susztak K . Epithelial Notch signaling regulates interstitial fibrosis development in the kidneys of mice and humans . The Journal of Clinical Investigation . 120 . 11 . 4040–54 . November 2010 . 20978353 . 2964979 . 10.1172/JCI43025 .
10. Pluskota E, Dowling JJ, Gordon N, Golden JA, Szpak D, West XZ, Nestor C, Ma YQ, Bialkowska K, Byzova T, Plow EF . The integrin coactivator kindlin-2 plays a critical role in angiogenesis in mice and zebrafish . Blood . 117 . 18 . 4978–87 . May 2011 . 21378273 . 3100704 . 10.1182/blood-2010-11-321182 .
11. Zhan J, Zhang H . Kindlins: Roles in development and cancer progression . The International Journal of Biochemistry & Cell Biology . 98 . 93–103 . May 2018 . 29544897 . 10.1016/j.biocel.2018.03.008 .
12. DOI = 10.1007/s00401-016-1652-z