TY - JOUR
T1 - The 19-amino acid insertion in the tumor-associated splice isoform Rac1b confers specific binding to p120 catenin
AU - Orlichenko, Lidiya
AU - Geyer, Rory
AU - Yanagisawa, Masahiro
AU - Khauv, Davitte
AU - Radisky, Evette S.
AU - Anastasiadis, Panos Z.
AU - Radisky, Derek C.
PY - 2010/6/18
Y1 - 2010/6/18
N2 - The Rac1b splice isoform contains a 19-amino acid insertion not found in Rac1; this insertion leads to decreased GTPase activity and reduced affinity for GDP, resulting in the intracellular predominance of GTP-bound Rac1b. Here, using co-precipitation and proteomic methods, we find that Rac1b does not bind to many common regulators of Rho family GTPases but that it does display enhanced binding to SmgGDS, RACK1, and p120 catenin (p120ctn), proteins involved in cell-cell adhesion, motility, and transcriptional regulation. We use molecular modeling and structure analysis approaches to determine that the interaction between Rac1b and p120ctn is dependent upon protein regions that are predicted to be unstructured in the absence of molecular complex formation, suggesting that the interaction between these two proteins involves coupled folding and binding. We also find that directed cell movement initiated by Rac1b is dependent upon p120. These results define a distinct binding functionality of Rac1b and provide insight into how the distinct phenotypic program activated by this protein may be implemented through molecular recognition of effectors distinct from those of Rac1.
AB - The Rac1b splice isoform contains a 19-amino acid insertion not found in Rac1; this insertion leads to decreased GTPase activity and reduced affinity for GDP, resulting in the intracellular predominance of GTP-bound Rac1b. Here, using co-precipitation and proteomic methods, we find that Rac1b does not bind to many common regulators of Rho family GTPases but that it does display enhanced binding to SmgGDS, RACK1, and p120 catenin (p120ctn), proteins involved in cell-cell adhesion, motility, and transcriptional regulation. We use molecular modeling and structure analysis approaches to determine that the interaction between Rac1b and p120ctn is dependent upon protein regions that are predicted to be unstructured in the absence of molecular complex formation, suggesting that the interaction between these two proteins involves coupled folding and binding. We also find that directed cell movement initiated by Rac1b is dependent upon p120. These results define a distinct binding functionality of Rac1b and provide insight into how the distinct phenotypic program activated by this protein may be implemented through molecular recognition of effectors distinct from those of Rac1.
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U2 - 10.1074/jbc.M109.099382
DO - 10.1074/jbc.M109.099382
M3 - Article
C2 - 20395297
AN - SCOPUS:77953508899
SN - 0021-9258
VL - 285
SP - 19153
EP - 19161
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 25
ER -