WFIKKN1 and WFIKKN2: "Companion" proteins regulating TGFB activity.
The WFIKKN (WAP, Follistatin/kazal, Immunoglobulin, Kunitz and Netrin domain-containing) protein family is composed of two multidomain proteins: WFIKKN1 and WFIKKN2. They were formed by domain shuffling and are likely present in deuterostoms. The WFIKKN (also called GASP) proteins are well known for their function in muscle and skeletal tissues, namely, inhibition of certain members of the transforming growth factor beta (TGFB) superfamily such as myostatin (MSTN) and growth and differentiation factor 11 (GDF11). However, the role of the WFIKKN proteins in other tissues is still poorly understood in spite of evidence suggesting possible action in the inner ear, brain and reproduction. Further, several recent studies based on next generation technologies revealed differential expression of WFIKKN1 and WFIKKN2 in various tissues suggesting that their function is not limited to MSTN and GDF11 inhibition in musculoskeletal tissue. In this review, we summarize current knowledge about the WFIKKN proteins and propose that they are "companion" proteins for various growth factors by providing localized and sustained presentation of TGFB proteins to their respective receptors, thus regulating the balance between the activation of Smad and non-Smad pathways by TGFB.
INRA, UR1037 Laboratory of Fish Physiology and Genomic, Growth and Flesh Quality Group, Campus de Beaulieu, 35000 Rennes, France. Electronic address: Olivier.Monestier@rennes.inra.fr.
Olivier
O
Monestier
INRA, UMR1061 Unité de Génétique Moléculaire Animale, 87060 Limoges, France; Université de Limoges, 87060 Limoges, France. Electronic address: veronique.blanquet@unilim.fr.
Véronique
V
Blanquet
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D000072417:Protein Domains; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism*
D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D016212:Transforming Growth Factor beta; C583826:WFIKKN1 protein, human; C424444:WFIKKN2 protein, human
GASP1; GASP2; Myostatin inhibitors; WFIKKN; WFIKKNRP