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)
Spinocerebellar ataxia type 10 (SCA10) is a dominantly inherited disorder caused by an intronic ATTCT pentanucleotide repeat expansion. The ATXN10 gene encodes a novel protein,
ataxin 10
, known previously as E46L, which is widely expressed in the brain. Ataxin 10 deficiency has been shown recently to cause increased apoptosis in primary cerebellar cultures, thus implicated in SCA10 pathogenesis. The biologic functions of
ataxin 10
remain largely unknown. By using yeast-two-hybrid screening of a human brain cDNA library, we identified the G-protein beta2 subunit (Gbeta2) as an
ataxin 10
binding partner, and the interaction was confirmed by coimmunoprecipitation and colocalization in mammalian cells in culture. Overexpression of
ataxin 10
in PC12 cells induced neurite extension and enhanced neuronal differentiation induced by nerve growth factor (NGF). Moreover, coexpression of
ataxin 10
and Gbeta2 potently activated the Ras-MAP kinase-Elk-1 cascade. Dominant negative Ras or inhibitor of
MEK
-1/2 (U0126) aborted this activation, and blocked morphologic changes, whereas inhibition of TrkA receptor by K252a had no effects. Our data suggest that the
ataxin 10
-Gbeta2 interaction represents a novel mechanism for inducing neuritogenesis in PC12 cells by activating the Ras-MAP kinase-Elk-1 cascade.
...
PMID:Ataxin 10 induces neuritogenesis via interaction with G-protein beta2 subunit. 1649 33
