Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P31749 (AKT)
 22,954 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glial cell line-derived neurotrophic factor (GDNF) family ligands are target-derived trophic factors for several neuronal subpopulations. They promote survival and neurite outgrowth through binding to specific members of the GDNF family receptor alpha (GFR alpha) and subsequent activation of the RET tyrosine kinase receptor. Using compartmentalized cultures of sympathetic neurons, we have studied the mechanism of GDNF retrograde signaling. Our results demonstrate the presence of GDNF receptors RET and GFR alpha 1 in the two cellular compartments, cell bodies and distal axons. Addition of GDNF to either compartment initiated local signaling, including activation of RET and its downstream effectors AKT and ERK1/2. Addition of GDNF to distal axons induced a retrograde signal leading to neuronal survival and neurite outgrowth. Retrograde signaling was associated with retrograde transport of radiolabeled GDNF and GFR alpha 1, as well as activation of RET and AKT, but not of ERK1/2, in cell bodies. No anterograde signal propagation or transport was observed. Our results suggest a general mechanism for retrograde signaling initiated at distal axons through tyrosine kinase receptors.
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PMID:Retrograde propagation of GDNF-mediated signals in sympathetic neurons. 1548 69

The RET tyrosine kinase receptor and its ligand, glial cell line-derived neurotrophic factor (GDNF) are critical regulators of renal and neural development. It has been demonstrated that RET activates a variety of downstream signaling cascades, including the RAS/mitogen-activated protein kinase and phosphatidylinositol-3-kinase(PI3-K)/AKT pathways. However, nuclear targets specific to RET-triggered signaling still remain elusive. We have previously identified a novel zinc finger protein, GZF1, whose expression is induced during GDNF/RET signaling and may play a role in renal branching morphogenesis. Here, we report the DNA binding property of GZF1 and its potential target gene. Using the cyclic amplification and selection of targets technique, the consensus DNA sequence to which GZF1 binds was determined. This sequence was found in the 5' regulatory region of the HOXA10 gene. Electrophoretic mobility shift assay revealed that GZF1 specifically binds to the determined consensus sequence and suppresses transcription of the luciferase gene from the HOXA10 gene regulatory element. These findings thus suggest that GZF1 may regulate the spatial and temporal expression of the HOXA10 gene which plays a role in morphogenesis.
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PMID:GDNF-inducible zinc finger protein 1 is a sequence-specific transcriptional repressor that binds to the HOXA10 gene regulatory region. 1604 25