%0 Journal Article %1 beaudry_involvement_2006 %A Beaudry, Hélène %A Gendron, Louis %A Guimond, Marie-Odile %A Payet, Marcel D %A Gallo-Payet, Nicole %D 2006 %J Endocrinology %K Angiotensin Angiotensin_{II} Carbazoles Cell_Division Cell_Line Indoles Neurites Neurons Protein_Kinase_C-alpha Receptor Signal_Transduction Type_2 rap1_{GTP-Binding}_Proteins {Mitogen-Activated}_Protein_Kinase_1 {Mitogen-Activated}_Protein_Kinase_3 {Proto-Oncogene}_Proteins_p21(ras) %N 9 %P 4263--4272 %R 10.1210/en.2006-0411 %T Involvement of protein kinase C alpha (PKC alpha) in the early action of angiotensin II type 2 (AT2) effects on neurite outgrowth in NG108-15 cells: AT2-receptor inhibits PKC alpha and p21ras activity %U http://www.ncbi.nlm.nih.gov/pubmed/16740968 %V 147 %X The aim of the present study was to investigate whether protein kinase C (PKC) isoforms may be among the putative candidates implicated in the primary effects of the Ang II type 2 (AT2) receptor. Western blot analyses revealed the presence of PKC alpha,epsilon, iota, and zeta in NG108-15 cells. After a 3-d treatment with 3 nm Gö6976, a specific inhibitor of classical PKC isoforms, cells were characterized by the presence of one elongated process similar to that observed after treatment with Ang II or with CGP42112, a selective AT2 receptor agonist. Similar findings were observed in cells expressing a dominant-negative mutant of PKC alpha (K368A). Inhibition of PKC alpha in NG108-15 cells also decreased cell number and proliferation. In conditions of acute stimulation, Ang II induced a time-dependent and transient inhibition of PKC alpha activity, as well as a decrease in PKC alpha levels associated with the membrane. Treatment of cells with Gö6976 was also found to inhibit p21(ras) (between 1-10 min) but stimulated Rap1 activity (1-5 min) in a time-course similar to that of Ang II. Incubation of NG108-15 cells with Gö6976 (3 nm) inhibited basal p42/p44(mapk) phosphorylation, but failed to interfere with its activation by the AT(2) receptor, indicating that inhibition of PKC alpha is not directly involved in the Rap1-MEK-p42/p44(mapk) cascade. Taken together, these results indicate that PKC alpha is a primary target of the AT2 receptor. Inhibition of PKC alpha leads to a decrease in both p21(ras) activity and cell proliferation, which may facilitate AT2 receptor signaling through p42/p44(mapk), thereby leading to neurite outgrowth.

@article{beaudry_involvement_2006, abstract = {The aim of the present study was to investigate whether protein kinase C {(PKC)} isoforms may be among the putative candidates implicated in the primary effects of the Ang {II} type 2 {(AT2)} receptor. Western blot analyses revealed the presence of {PKC} alpha,epsilon, iota, and zeta in {NG108-15} cells. After a 3-d treatment with 3 nm Gö6976, a specific inhibitor of classical {PKC} isoforms, cells were characterized by the presence of one elongated process similar to that observed after treatment with Ang {II} or with {CGP42112}, a selective {AT2} receptor agonist. Similar findings were observed in cells expressing a dominant-negative mutant of {PKC} alpha {(K368A).} Inhibition of {PKC} alpha in {NG108-15} cells also decreased cell number and proliferation. In conditions of acute stimulation, Ang {II} induced a time-dependent and transient inhibition of {PKC} alpha activity, as well as a decrease in {PKC} alpha levels associated with the membrane. Treatment of cells with Gö6976 was also found to inhibit p21(ras) (between 1-10 min) but stimulated Rap1 activity (1-5 min) in a time-course similar to that of Ang {II.} Incubation of {NG108-15} cells with Gö6976 (3 nm) inhibited basal p42/p44(mapk) phosphorylation, but failed to interfere with its activation by the {AT(2)} receptor, indicating that inhibition of {PKC} alpha is not directly involved in the {Rap1-MEK-p42/p44(mapk)} cascade. Taken together, these results indicate that {PKC} alpha is a primary target of the {AT2} receptor. Inhibition of {PKC} alpha leads to a decrease in both p21(ras) activity and cell proliferation, which may facilitate {AT2} receptor signaling through p42/p44(mapk), thereby leading to neurite outgrowth.}, added-at = {2011-08-03T21:06:35.000+0200}, author = {Beaudry, Hélène and Gendron, Louis and Guimond, {Marie-Odile} and Payet, Marcel D and {Gallo-Payet}, Nicole}, biburl = {https://www.bibsonomy.org/bibtex/295aa3ab200638faaecf788e5657ba10f/crc_chus}, doi = {10.1210/en.2006-0411}, interhash = {29e75ef50b5f00b9fbfe7fc8d5b61271}, intrahash = {95aa3ab200638faaecf788e5657ba10f}, issn = {0013-7227}, journal = {Endocrinology}, keywords = {Angiotensin Angiotensin_{II} Carbazoles Cell_Division Cell_Line Indoles Neurites Neurons Protein_Kinase_C-alpha Receptor Signal_Transduction Type_2 rap1_{GTP-Binding}_Proteins {Mitogen-Activated}_Protein_Kinase_1 {Mitogen-Activated}_Protein_Kinase_3 {Proto-Oncogene}_Proteins_p21(ras)}, month = sep, note = {{PMID:} 16740968}, number = 9, pages = {4263--4272}, shorttitle = {Involvement of protein kinase C alpha {(PKC} alpha) in the early action of angiotensin {II} type 2 {(AT2)} effects on neurite outgrowth in {NG108-15} cells}, timestamp = {2011-08-03T21:10:03.000+0200}, title = {Involvement of protein kinase C alpha {(PKC} alpha) in the early action of angiotensin {II} type 2 {(AT2)} effects on neurite outgrowth in {NG108-15} cells: {AT2-receptor} inhibits {PKC} alpha and p21ras activity}, url = {http://www.ncbi.nlm.nih.gov/pubmed/16740968}, volume = 147, year = 2006 }