TY - JOUR
T1 - A role for she, Grb2, and Raf-1 in FcγRI signal relay
AU - Park, Rae Kil
AU - Liu, Yenbou
AU - Durden, Donald L.
PY - 1996
Y1 - 1996
N2 - The activation of the serine/threonine kinase, Raf-1, serves to connect upstream protein tyrosine kinases to downstream signaling events. We previously reported that FcγRI stimulation of Interferon γ-differentiated U937 cells (termed U937IF cells) induces a mobility shift in Erk2. Herein, we report that cross-linking of FcγRI receptor in U937IF cells induces a marked tyrosine phosphorylation of Raf-1 (10-fold increase). Tyrosine phosphorylation of Raf-1 is induced by FcγRI activation and not by PMA (1 μg/ml), N-formyl-Met-Leu-Phe (1 μM), calcium ionophore (1 μM), thrombin (0.05 unit/ml), FcγRII, or FcγRIII stimulation. The kinetics of Raf-1 tyrosine phosphorylation is rapid, reaching peak levels 1-2 min after FcγRI activation, and the tyrosine phosphorylation of Raf-1 precedes the activation of the respiratory burst. FcγRI cross-linking induces the tyrosine phosphorylation of Shc; tyrosine-phosphorylated She binds to Grb2 forming a Shc-Grb2 complex. The data provide evidence that the FcγRI receptor signals via the upstream activation of nonreceptor protein tyrosine kinases, which leads to the subsequent activation of Ras family GTPases and serine/threonine kinases, Raf-1 and mitogen-activated protein kinase.
AB - The activation of the serine/threonine kinase, Raf-1, serves to connect upstream protein tyrosine kinases to downstream signaling events. We previously reported that FcγRI stimulation of Interferon γ-differentiated U937 cells (termed U937IF cells) induces a mobility shift in Erk2. Herein, we report that cross-linking of FcγRI receptor in U937IF cells induces a marked tyrosine phosphorylation of Raf-1 (10-fold increase). Tyrosine phosphorylation of Raf-1 is induced by FcγRI activation and not by PMA (1 μg/ml), N-formyl-Met-Leu-Phe (1 μM), calcium ionophore (1 μM), thrombin (0.05 unit/ml), FcγRII, or FcγRIII stimulation. The kinetics of Raf-1 tyrosine phosphorylation is rapid, reaching peak levels 1-2 min after FcγRI activation, and the tyrosine phosphorylation of Raf-1 precedes the activation of the respiratory burst. FcγRI cross-linking induces the tyrosine phosphorylation of Shc; tyrosine-phosphorylated She binds to Grb2 forming a Shc-Grb2 complex. The data provide evidence that the FcγRI receptor signals via the upstream activation of nonreceptor protein tyrosine kinases, which leads to the subsequent activation of Ras family GTPases and serine/threonine kinases, Raf-1 and mitogen-activated protein kinase.
UR - http://www.scopus.com/inward/record.url?scp=0029920272&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029920272&partnerID=8YFLogxK
U2 - 10.1074/jbc.271.23.13342
DO - 10.1074/jbc.271.23.13342
M3 - Article
C2 - 8662746
AN - SCOPUS:0029920272
VL - 271
SP - 13342
EP - 13348
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 23
ER -