Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
Compound
Query: EC:2.5.1.18 (
glutathione S-transferase
)
22,582
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
G protein-regulated inducer of neurite outgrowth 1
(
GRIN1
) was initially identified as a binding protein for guanosine 5'-3-O-(thio)triphosphate-bound Galphaz.
GRIN1
is specifically expressed in brain and interacts selectively with activated alpha subunits of the Gi subfamily.
GRIN1
colocalizes with Galphao at the growth cone of neuronal cells and promotes neurite extension in Neuro2a cells when coexpressed with constitutively active mutant GalphaoQ205L. These results suggest that
GRIN1
functions as a downstream target for Galphao. However,
GRIN1
does not contain domains that are homologous to known signaling motifs. To understand the mechanisms of Galphao-
GRIN1
pathway, we analyzed functional domains of
GRIN1
that are involved in binding with Galphao or with its targeting to the plasma membrane. Using pull-down assays with
glutathione S-transferase
-fused
GRIN1
deletion mutants, Galphao binding regions were localized to amino acid residues 716 to 746 and 797 to 827 of
GRIN1
. The Galphao binding region of
GRIN1
did not demonstrate GTPase accelerating activity for Galphao.
GRIN1
localized in the cell periphery in Neuro2a cells, and two cysteine residues at C-terminal region of
GRIN1
(Cys818 and Cys819) were shown to be critical for its membrane targeting. Coexpression of
GRIN1
with GalphaoQ205L or GRIN1Delta(717-827), which lacks Galphao binding region, promoted microspike formation in Swiss 3T3 cells or neurite extension in Neuro2a cells. The dominant-negative mutant of Cdc42 blocked these morphological changes. Coexpression of
GRIN1
and GalphaoQ205L stimulated the formation of GTP-bound Cdc42 in Swiss 3T3 cells. These results suggest that the binding of activated Galphao to
GRIN1
induces activation of Cdc42, which leads to morphological changes in neuronal cells.
...
PMID:Functional characterization of Galphao signaling through G protein-regulated inducer of neurite outgrowth 1. 1558 44
