Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2000-11-14
pubmed:abstractText
The small G-protein Ras, a critical component in the signalling pathways regulating cell growth, is involved in the tonic upregulation of voltage-dependent calcium channels (VDCCs) in rat sensory neurones. To investigate which downstream effector(s) of Ras is involved in this process, a series of Ras mutant cDNAs were co-expressed with green fluorescent protein (GFP) in primary cultured rat dorsal root ganglion neurones (DRGs). Constitutively active V12Ras (glycine 12 to valine) markedly increased basal calcium current density by 41 % compared with control cells (GFP alone). In contrast, a farnesylation-defective mutant, V12S186Ras (cysteine 186 to serine; activates no downstream effectors), significantly reduced calcium current density by 47 %. Ras effector region mutants V12C40 (tyrosine 40 to cysteine; activates the p110 alpha-subunit of phosphatidylinositol 3-kinase) and V12G37 (glutamic acid 37 to glycine; activates Ral guanine nucleotide dissociation stimulator) had no significant effect on VDCC current. However, V12S35Ras (threonine 35 to serine; activates Raf-1 and the mitogen-activated protein kinase (MAPK) pathway) markedly increased basal calcium current density by 67 %, suggesting that Raf-1 activation is sufficient for Ras enhancement of calcium current in these cells. Raf-1 activates MEK (MAPK kinase) in the MAPK pathway, and the MEK inhibitor U0126 reduced calcium current by 45 % after 10-15 min, whereas the inactive analogue U0124 had no effect. This rapid time course for MEK inhibition suggests direct modulation of VDCCs via the Ras-MAPK pathway rather than gene expression-mediated effects. The relative proportions of omega-conotoxin GVIA- and nicardipine-sensitive N- ( approximately 40 %) and L- ( approximately 40 %) type currents were unaffected by either V12S35Ras expression or U0126 pre-treatment, suggesting that all components of calcium current in DRGs, are enhanced via this pathway.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-10066247, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-10336467, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-10480934, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-10525060, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-1323671, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-1374458, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-1380963, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-1524830, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-1652268, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-1654419, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-1657056, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-1918164, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-2208277, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-2434853, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-2560650, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-3005866, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-3681406, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-6089200, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-7540671, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-7722647, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-7791875, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-7867061, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-7910202, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-7910846, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-7980500, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-8106507, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-8226808, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-8332195, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-8334704, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-8626482, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-8628998, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-8710373, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-8747236, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-8789937, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-8791426, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-9150145, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-9192891, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-9215709, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-9338074, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-9660836, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-9685325, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-9744944, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-9753087, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-9852579, http://linkedlifedata.com/resource/pubmed/commentcorrection/10990531-9950427
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-3751
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
527 Pt 3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
433-44
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
More...