TY - JOUR
T1 - Differential interaction of Enigma protein with the two RET isoforms
AU - Borrello, Maria Grazia
AU - Mercalli, Elena
AU - Perego, Carla
AU - Degl'Innocenti, Debora
AU - Ghizzoni, Simona
AU - Arighi, Elena
AU - Eroini, Barbara
AU - Rizzetti, Maria Grazia
AU - Pierotti, Marco A.
PY - 2002
Y1 - 2002
N2 - The receptor tyrosine kinase RET, with a known role in embryonic development and in human pathologies, is alternatively spliced to yield at least two functional isoforms, which differ only in their carboxyl terminal. Enigma protein is a member of the PDZ-LIM family and is known to interact with the short isoform of RET/PTC2, a chimeric oncoprotein isolated from papillary thyroid carcinoma. Here, we show that Enigma also interacts in intact cells with the short isoform of RET-wt and of its pathologic mutants associated to MEN2 syndromes, RET-C634R and RET-M918T. In contrast, Enigma binds all the corresponding RET long isoforms very poorly and colocalizes with short but not long RET/PTC2 isoforms. The RET docking tyrosine for Enigma is the last but one before the divergence between the two isoforms and we demonstrated that short-isoform-specific amino acid residues +2 to +4 to this tyrosine are required for the interaction of RET/PTC2 with Enigma.
AB - The receptor tyrosine kinase RET, with a known role in embryonic development and in human pathologies, is alternatively spliced to yield at least two functional isoforms, which differ only in their carboxyl terminal. Enigma protein is a member of the PDZ-LIM family and is known to interact with the short isoform of RET/PTC2, a chimeric oncoprotein isolated from papillary thyroid carcinoma. Here, we show that Enigma also interacts in intact cells with the short isoform of RET-wt and of its pathologic mutants associated to MEN2 syndromes, RET-C634R and RET-M918T. In contrast, Enigma binds all the corresponding RET long isoforms very poorly and colocalizes with short but not long RET/PTC2 isoforms. The RET docking tyrosine for Enigma is the last but one before the divergence between the two isoforms and we demonstrated that short-isoform-specific amino acid residues +2 to +4 to this tyrosine are required for the interaction of RET/PTC2 with Enigma.
KW - Enigma
KW - Oncoproteins
KW - RET
KW - RET isoforms
KW - Tyrosine kinase
UR - http://www.scopus.com/inward/record.url?scp=0036384286&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036384286&partnerID=8YFLogxK
U2 - 10.1016/S0006-291X(02)00886-0
DO - 10.1016/S0006-291X(02)00886-0
M3 - Article
C2 - 12176011
AN - SCOPUS:0036384286
VL - 296
SP - 515
EP - 522
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -