TY - JOUR
T1 - The Shp-1 and Shp-2, tyrosine phosphatases, are recruited on cell membrane in two distinct molecular complexes including Ret oncogenes
AU - Incoronato, Mariarosaria
AU - D'Alessio, Amelia
AU - Paladino, Simona
AU - Zurzolo, Chiara
AU - Carlomagno, Maria Stella
AU - Cerchia, Laura
AU - De Franciscis, Vittorio
PY - 2004/7
Y1 - 2004/7
N2 - The Shp-2 and Shp-1 non-transmembrane tyrosine phosphatases display different and even opposing effects on downstream signaling events initiated by Ret activation. By using rat pheochromocytoma-derived PC12 cells, here we studied the interactions of Shp-2 and Shp-1 with two activated mutants of Ret receptor, RetC634Y and RetM918T. Each of these mutated receptors causes inheritance of distinct cancer syndromes, multiple endocrine neoplasia (MEN) type 2A and type 2B, respectively. We show that: (i) both Shp-1 and Shp-2 are associated to a multiprotein complex that includes Ret mutants; (ii) the Shp-1-Ret complexes are distinct from Shp-2-Ret complexes, and these complexes are differently distributed inside and outside lipid rafts; (iii) constitutively activated Ret proteins neither directly bind to nor are substrates of these phosphatases. Our results well support the evidence that Ret complexes within and outside rafts mediate distinct biological functions, and indicate that the presence of either Shps participates to determine such functions.
AB - The Shp-2 and Shp-1 non-transmembrane tyrosine phosphatases display different and even opposing effects on downstream signaling events initiated by Ret activation. By using rat pheochromocytoma-derived PC12 cells, here we studied the interactions of Shp-2 and Shp-1 with two activated mutants of Ret receptor, RetC634Y and RetM918T. Each of these mutated receptors causes inheritance of distinct cancer syndromes, multiple endocrine neoplasia (MEN) type 2A and type 2B, respectively. We show that: (i) both Shp-1 and Shp-2 are associated to a multiprotein complex that includes Ret mutants; (ii) the Shp-1-Ret complexes are distinct from Shp-2-Ret complexes, and these complexes are differently distributed inside and outside lipid rafts; (iii) constitutively activated Ret proteins neither directly bind to nor are substrates of these phosphatases. Our results well support the evidence that Ret complexes within and outside rafts mediate distinct biological functions, and indicate that the presence of either Shps participates to determine such functions.
KW - GDNF
KW - glial cell line-derived neurotrophic factor
KW - glutathione S-transferase
KW - GST
KW - Lipid rafts
KW - MEN
KW - MEN2
KW - multiple endocrine neoplasia
KW - Oncogene
KW - PC12
KW - Ret
KW - SH2-containing tyrosine phosphatase 1
KW - SH2-containing tyrosine phosphatase 2
KW - Shp-1
KW - Shp-2
UR - http://www.scopus.com/inward/record.url?scp=2042443795&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=2042443795&partnerID=8YFLogxK
U2 - 10.1016/j.cellsig.2004.01.002
DO - 10.1016/j.cellsig.2004.01.002
M3 - Article
C2 - 15115663
AN - SCOPUS:2042443795
VL - 16
SP - 847
EP - 856
JO - Cellular Signalling
JF - Cellular Signalling
SN - 0898-6568
IS - 7
ER -