TY - JOUR
T1 - The adaptor function of SHP-2 downstream of the prolactin receptor is required for the recruitment of p29, a substrate of SHP-2
AU - Minoo, Parham
AU - Chughtai, Naila
AU - Campiglio, Manuela
AU - Stein-Gerlach, Matthias
AU - Lebrun, Jean Jacques
AU - Ullrich, Axel
AU - Ali, Suhad
PY - 2003/3/1
Y1 - 2003/3/1
N2 - SHP-2, a cytosolic protein tyrosine phosphatase with two SH2 domains and multiple tyrosine phosphorylation sites, contributes to signal transduction as an enzyme and/or adaptor molecule. Here we demonstrate that prolactin (PRL) stimulation of the PRL-responsive Nb2 cells, a rat lymphoma cell line, and T47D cells, a human breast cancer cell line, lead to the complex formation of SHP-2 and growth factor receptor-bound protein-2 (grb2). Using transient co-overexpression studies of the prolactin receptor (PRLR) and several tyrosine to phenylalanine mutants of SHP-2, we show that grb2 associates with SHP-2 through the C-terminal tyrosine residues of SHP-2, Y546 and Y584. Furthermore, in this study, we found a highly phosphorylated, 29-kDa protein (p29), a substrate of SHP-2. The recruitment of p29 to SHP-2 requires the carboxy-terminal tyrosine residues of SHP-2 (Y546 and Y584). Together, our results indicate that SHP-2 may function as an adaptor molecule downstream of the PRLR and highlight a new recruitment mechanism of SHP-2 substrates.
AB - SHP-2, a cytosolic protein tyrosine phosphatase with two SH2 domains and multiple tyrosine phosphorylation sites, contributes to signal transduction as an enzyme and/or adaptor molecule. Here we demonstrate that prolactin (PRL) stimulation of the PRL-responsive Nb2 cells, a rat lymphoma cell line, and T47D cells, a human breast cancer cell line, lead to the complex formation of SHP-2 and growth factor receptor-bound protein-2 (grb2). Using transient co-overexpression studies of the prolactin receptor (PRLR) and several tyrosine to phenylalanine mutants of SHP-2, we show that grb2 associates with SHP-2 through the C-terminal tyrosine residues of SHP-2, Y546 and Y584. Furthermore, in this study, we found a highly phosphorylated, 29-kDa protein (p29), a substrate of SHP-2. The recruitment of p29 to SHP-2 requires the carboxy-terminal tyrosine residues of SHP-2 (Y546 and Y584). Together, our results indicate that SHP-2 may function as an adaptor molecule downstream of the PRLR and highlight a new recruitment mechanism of SHP-2 substrates.
KW - Grb2
KW - Jak/Stat
KW - Phosphatase
KW - Prolactin
KW - Prolactin receptor
KW - SHP-2
KW - Tyrosine phosphorylation
UR - http://www.scopus.com/inward/record.url?scp=0037345038&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037345038&partnerID=8YFLogxK
U2 - 10.1016/S0898-6568(02)00122-5
DO - 10.1016/S0898-6568(02)00122-5
M3 - Article
C2 - 12531430
AN - SCOPUS:0037345038
VL - 15
SP - 319
EP - 326
JO - Cellular Signalling
JF - Cellular Signalling
SN - 0898-6568
IS - 3
ER -