WASF1 explained

Wiskott–Aldrich syndrome protein family member 1, also known as WASP-family verprolin homologous protein 1 (WAVE1), is a protein that in humans is encoded by the WASF1 gene.^{[1] [2] [3]}

Function

The protein encoded by this gene, a member of the Wiskott–Aldrich syndrome protein (WASP) family, plays a critical role downstream of Rac, a Rho-family small GTPase, through its involvement in the WAVE regulatory complex in regulating the actin cytoskeleton required for membrane ruffling. It has been shown to associate with an actin nucleation core Arp2/3 complex while enhancing actin polymerization in vitro.

Clinical significance

Wiskott–Aldrich syndrome is a disease of the immune system, likely due to defects in regulation of actin cytoskeleton.^[3]

Interactions

WASF1 has been shown to interact with BAIAP2^[4] and Profilin 1.^[1]

Further reading

• Sloane JA, Vartanian TK . WAVE1 and regulation of actin nucleation in myelination. . The Neuroscientist . 13 . 5 . 486–91 . 2007 . 17901257 . 10.1177/1073858407299423 . 295778 .
• Whitebread S, Mele M, Kamber B, de Gasparo M . Preliminary biochemical characterization of two angiotensin II receptor subtypes. . Biochem. Biophys. Res. Commun. . 163 . 1 . 284–91 . 1989 . 2775266 . 10.1016/0006-291X(89)92133-5 .
• Kitamura T, Kitamura Y, Yonezawa K, etal . Molecular cloning of p125Nap1, a protein that associates with an SH3 domain of Nck. . Biochem. Biophys. Res. Commun. . 219 . 2 . 509–14 . 1996 . 8605018 . 10.1006/bbrc.1996.0264 . 20.500.14094/D1001555 . free .
• Nagase T, Seki N, Ishikawa K, etal . Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain. . DNA Res. . 3 . 5 . 321–9, 341–54 . 1997 . 9039502 . 10.1093/dnares/3.5.321 . free .
• She HY, Rockow S, Tang J, etal . Wiskott–Aldrich syndrome protein is associated with the adapter protein Grb2 and the epidermal growth factor receptor in living cells. . Mol. Biol. Cell . 8 . 9 . 1709–21 . 1997 . 9307968 . 10.1091/mbc.8.9.1709. 305731 .
• Witke W, Podtelejnikov AV, Di Nardo A, etal . In mouse brain profilin I and profilin II associate with regulators of the endocytic pathway and actin assembly. . EMBO J. . 17 . 4 . 967–76 . 1998 . 9463375 . 10.1093/emboj/17.4.967 . 1170446 .
• Bear JE, Rawls JF, Saxe CL . SCAR, a WASP-related protein, isolated as a suppressor of receptor defects in late Dictyostelium development. . J. Cell Biol. . 142 . 5 . 1325–35 . 1998 . 9732292 . 10.1083/jcb.142.5.1325 . 2149354 .
• Wu Y, Dowbenko D, Lasky LA . PSTPIP 2, a second tyrosine phosphorylated, cytoskeletal-associated protein that binds a PEST-type protein-tyrosine phosphatase. . J. Biol. Chem. . 273 . 46 . 30487–96 . 1998 . 9804817 . 10.1074/jbc.273.46.30487 . free .
• Suetsugu S, Miki H, Takenawa T . Identification of two human WAVE/SCAR homologues as general actin regulatory molecules which associate with the Arp2/3 complex. . Biochem. Biophys. Res. Commun. . 260 . 1 . 296–302 . 1999 . 10381382 . 10.1006/bbrc.1999.0894 .
• Banin S, Gout I, Brickell P . Interaction between Wiskott–Aldrich Syndrome protein (WASP) and the Fyn protein-tyrosine kinase. . Mol. Biol. Rep. . 26 . 3 . 173–7 . 1999 . 10532312 . 10.1023/A:1006954206151 . 36018089 .
• Higgs HN, Blanchoin L, Pollard TD . Influence of the C terminus of Wiskott–Aldrich syndrome protein (WASp) and the Arp2/3 complex on actin polymerization. . Biochemistry . 38 . 46 . 15212–22 . 1999 . 10563804 . 10.1021/bi991843 .
• Westphal RS, Soderling SH, Alto NM, etal . Scar/WAVE-1, a Wiskott–Aldrich syndrome protein, assembles an actin-associated multi-kinase scaffold. . EMBO J. . 19 . 17 . 4589–600 . 2000 . 10970852 . 10.1093/emboj/19.17.4589 . 302050 .
• Prehoda KE, Scott JA, Mullins RD, Lim WA . Integration of multiple signals through cooperative regulation of the N-WASP-Arp2/3 complex. . Science . 290 . 5492 . 801–6 . 2000 . 11052943 . 10.1126/science.290.5492.801 . 2000Sci...290..801P .
• Miki H, Yamaguchi H, Suetsugu S, Takenawa T . IRSp53 is an essential intermediate between Rac and WAVE in the regulation of membrane ruffling. . Nature . 408 . 6813 . 732–5 . 2001 . 11130076 . 10.1038/35047107 . 2000Natur.408..732M . 4426046 .
• Marchand JB, Kaiser DA, Pollard TD, Higgs HN . Interaction of WASP/Scar proteins with actin and vertebrate Arp2/3 complex. . Nat. Cell Biol. . 3 . 1 . 76–82 . 2001 . 11146629 . 10.1038/35050590 . 30437883 .
• Eden S, Rohatgi R, Podtelejnikov AV, etal . Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck. . Nature . 418 . 6899 . 790–3 . 2002 . 12181570 . 10.1038/nature00859 . 2002Natur.418..790E . 4350733 .
• Yarar D, D'Alessio JA, Jeng RL, Welch MD . Motility determinants in WASP family proteins. . Mol. Biol. Cell . 13 . 11 . 4045–59 . 2003 . 12429845 . 10.1091/mbc.E02-05-0294 . 133613 .
• Soderling SH, Binns KL, Wayman GA, etal . The WRP component of the WAVE-1 complex attenuates Rac-mediated signalling. . Nat. Cell Biol. . 4 . 12 . 970–5 . 2003 . 12447388 . 10.1038/ncb886 . 1423222 .

Notes and References

1. Miki H, Suetsugu S, Takenawa T . WAVE, a novel WASP-family protein involved in actin reorganization induced by Rac . EMBO J . 17 . 23 . 6932–41 . February 1999 . 9843499 . 1171041 . 10.1093/emboj/17.23.6932 .
2. Machesky LM, Insall RH . Scar1 and the related Wiskott–Aldrich syndrome protein, WASP, regulate the actin cytoskeleton through the Arp2/3 complex . Curr Biol . 8 . 25 . 1347–56 . March 1999 . 9889097 . 10.1016/S0960-9822(98)00015-3 . 16661755 . free .
3. Web site: Entrez Gene: WASF1 WAS protein family, member 1.
4. Miki H, Yamaguchi H, Suetsugu S, Takenawa T . IRSp53 is an essential intermediate between Rac and WAVE in the regulation of membrane ruffling . Nature . 408 . 6813 . 732–5 . December 2000 . 11130076 . 10.1038/35047107 . 2000Natur.408..732M . 4426046 .