TY - JOUR
T1 - The action of v-src on gap junctional permeability is modulated by pH
AU - Hyrc, K.
AU - Rose, B.
PY - 1990
Y1 - 1990
N2 - The product of the viral src gene (v-src) is the protein tyrosine kinase pp60(v-src). Among the known consequences of pp60(v-src) activity is the reduction in permeability of gap junctions, an effect that is counteracted by the calcium antagonist TMB-8 (8-N,N-[diethylamino]octyl-3,4,5-trimethoxybenzoate). We show here that a decrease in intracellular pH (pH(i)) also counteracts the v-src effect: junctional permeability of cells containing active v-src kinase rose with decreasing pH(i) in the range 7.15 to 6.75, whereas junctional permeability of cells containing inactive v-src kinase or no v-src at all was insensitive to pH in that range. Low pH also counteracted the known action of diacylglycerol on junction, but only when pp60(v-src) kinase was inactive. Immunoblots of whole-cell lysates using an antibody against phosphotyrosine show that phosphorylation on tyrosine of at least one cellular protein, specific for pp60(v-src) kinase activity, was reduced by low pH but not by TMB-8. These results suggest that TMB-8 does not inhibit v-src action on junctional permeability by interfering with tyrosine phosphorylation of a protein crucial for closure of gap junction channels, but that the inhibition by low pH may be via this mechanism.
AB - The product of the viral src gene (v-src) is the protein tyrosine kinase pp60(v-src). Among the known consequences of pp60(v-src) activity is the reduction in permeability of gap junctions, an effect that is counteracted by the calcium antagonist TMB-8 (8-N,N-[diethylamino]octyl-3,4,5-trimethoxybenzoate). We show here that a decrease in intracellular pH (pH(i)) also counteracts the v-src effect: junctional permeability of cells containing active v-src kinase rose with decreasing pH(i) in the range 7.15 to 6.75, whereas junctional permeability of cells containing inactive v-src kinase or no v-src at all was insensitive to pH in that range. Low pH also counteracted the known action of diacylglycerol on junction, but only when pp60(v-src) kinase was inactive. Immunoblots of whole-cell lysates using an antibody against phosphotyrosine show that phosphorylation on tyrosine of at least one cellular protein, specific for pp60(v-src) kinase activity, was reduced by low pH but not by TMB-8. These results suggest that TMB-8 does not inhibit v-src action on junctional permeability by interfering with tyrosine phosphorylation of a protein crucial for closure of gap junction channels, but that the inhibition by low pH may be via this mechanism.
UR - http://www.scopus.com/inward/record.url?scp=0025217098&partnerID=8YFLogxK
U2 - 10.1083/jcb.110.4.1217
DO - 10.1083/jcb.110.4.1217
M3 - Article
C2 - 2157717
AN - SCOPUS:0025217098
SN - 0021-9525
VL - 110
SP - 1217
EP - 1226
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 4
ER -