Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.12.2 (
MEK
)
18,161
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Differentiation of neuronal precursor cells in response to neurotrophic differentiation factors is accompanied by the activation of membrane-anchored SNT signaling adaptor proteins. Two classes of differentiation factors, the neurotrophins and fibroblast growth factors, induce rapid tyrosine phosphorylation of
SNT1
(FRS2alpha), which in turn enables
SNT1
to recruit Shp2 tyrosine phosphatase and Grb2 adaptor protein in complex with the Ras GDP/GTP exchange factor Sos. To determine effector functions of SNT that promote neuronal differentiation of PC12 pheochromocytoma cells, we engineered a chimeric protein,
SNT1
(IRS)CX, bearing the effector region of
SNT1
and the insulin receptor recognition domains of IRS2. Insulin promoted tyrosine phosphorylation of
SNT1
(IRS)CX in transfected PC12 cells accompanied by sustained activation of ERK1/2 mitogen-activated protein kinases and neuronal differentiation. The
SNT1
(IRS)CX-mediated response was dependent on endogenous Ras,
MEK
, and Shp2 activities. Mutagenesis of
SNT1
(IRS)CX identified three classes of effector motifs within SNT critical for both sustained ERK activation and neuronal differentiation: 1) four phosphotyrosine motifs that mediate recruitment of Grb2, 2) two phosphotyrosine motifs that mediate recruitment of Shp2, and 3) a C-terminal motif that functions by helping to recruit Sos. We discuss possible mechanisms by which three functionally distinct SNT effector motifs collaborate to promote a downstream biochemical and biological response.
...
PMID:Multiple effector domains within SNT1 coordinate ERK activation and neuronal differentiation of PC12 cells. 1127 83
