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The FWD1/β‐TrCP‐mediated degradation pathway establishes a ‘turning off switch’ of a Cdc42 guanine nucleotide exchange factor, FGD1
Author(s) -
Hayakawa Makio,
Kitagawa Hideo,
Miyazawa Keiji,
Kitagawa Masatoshi,
Kikugawa Kiyomi
Publication year - 2005
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2005.00834.x
Subject(s) - guanine nucleotide exchange factor , ubiquitin ligase , biology , ubiquitin , cdc42 , serine , microbiology and biotechnology , phosphorylation , biochemistry , gtpase , gene
FWD1/β‐TrCP is the F‐box protein that functions as the receptor subunit of the SCF FWD1/β‐TrCP ubiquitin ligase and has been shown to be responsible for the degradation of important signaling molecules such as IκBs and β‐catenin. Protein substrates of FWD1/β‐TrCP contain a consensus DSGΨXS motif (where Ψ represents a hydrophobic residue and X represents any amino acid). Recognition by FWD1/β‐TrCP requires phosphorylation of the conserved serines in that motif. Here we show that FGD1, a Cdc42 guanine nucleotide exchange factor (GEF), is a novel target of the SCF FWD1/β‐TrCP ubiquitin ligase. A mutant FGD1 protein, FGD1(SA), in which both of the critical serine residues in the DSGΨXS motif have been replaced by alanines, does not interact with FWD1/β‐TrCP and exhibits increased stability. Morphological changes induced by wild‐type FGD1 (FGD1(WT)) are reduced by the co‐expression of SCF FWD1/β‐TrCP whereas those induced by FGD1(SA) are not affected. FGD1(SA)‐expressing cells show a higher level of cell motility than FGD1(WT)‐expressing cells. We present a novel ‘turning off’ mechanism for the inactivation of FGD1, an upstream regulator for Cdc42.