Dhj. Vanweering et al., RET RECEPTOR TYROSINE KINASE ACTIVATES EXTRACELLULAR SIGNAL-REGULATEDKINASE-2 IN SK-N-MC CELLS, Oncogene, 11(11), 1995, pp. 2207-2214
Ret is a receptor tyrosine kinase predominantly expressed in tissue de
rived from the neuroectoderm and is involved in multiple endocrine neo
plasia type 2A and 2B, familiar medullary thyroid carcinoma, and Hirsc
hsprung's disease, The ligand for the receptor is still unknown, Previ
ously, using a human epidermal growth factor receptor - Ret chimaeric
receptor (HERRet) stably transfected into fibroblasts, it was shown th
at Pet activation induces the activation of p21ras, but, surprisingly,
activation of extracellular signal-regulated kinase 2 (ERK2) was not
observed (Santoro et al, (1994), Mol. Cell, Biol., 14, 663), In this r
eport we describe early signaling events induced by the activated HERR
et fusion receptor in a cell line derived from neuroectodermal tissue,
SK-N-MC, In these cells, activated HERRet induces tyrosine phosphoryl
ation of She, complex formation of She with Grb2 and Sos and activatio
n of p21ras, Importantly, also ERK2 is activated, This activation was
strong and sustained for at least 2 h, Activation was abolished by the
dominant negative p21ras(asn17) mutant, showing that activation of ER
K2 is mediated by p21ras, These results suggest that Pet can induce ER
K2 activation in a p21ras dependent manner in cells derived from tissu
e where Pet is endogenously expressed.