Galpha13 regulation of proto-Dbl signaling.
Rho family GTPases play important roles in the regulation of intracellular signals induced by activated heterotrimeric G proteins of the alpha(12/13) family. The alpha(12/13) subunits activate Rho GTPases through direct binding to a group of Rho guanine nucleotide exchange factors (GEFs) characterized by the presence of a G protein signaling-like (RGL) domain. The Rho GEF proto-Dbl, that does not contain a RGL domain, was also found to link Galpha(12/13) signals to Rho. We have explored the effects of activated Galpha(13) and Galpha(13)-associated G protein-coupled receptor (GPCR) agonists on proto-Dbl regulation. We show that activated Galpha(13), but not Galpha(12) or Galpha(q), induces translocation of proto-Dbl to the cell membrane with consequent enlargement of cell body and membrane ruffling. These effects were evident also when Galpha(13)-associated GPCR agonists were used on cells expressing proto-Dbl and were accompanied by the activation of Cdc42 and RhoA GTPases and further downstream effector JNK and p38 kinases. Moreover, we show that both activated Galpha(13) and GPCR agonists stimulate proto-Dbl interaction with ezrin to promote ezrin translocation to the plasma membrane. These results suggest a mechanism by which proto-Dbl and its effector pathways are regulated by Galpha(13)-mediated signals through association with ezrin.
Vanni
Cristina
C
Laboratorio di Biologia Molecolare, Istituto G. Gaslini, Genova, Italy.
Mancini
Patrizia
P
Ottaviano
Catherine
C
Ognibene
Marzia
M
Parodi
Alessia
A
Merello
Elisa
E
Russo
Chiara
C
Varesio
Luigi
L
Zheng
Yi
Y
Torrisi
Maria Rosaria
MR
Eva
Alessandra
A
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D015153:Blotting, Western; D001920:Bradykinin / Q000494:pharmacology; D019556:COS Cells; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D047468:Immunoprecipitation; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008246:Lysophospholipids / Q000494:pharmacology; D051379:Mice; D041681:NIH 3T3 Cells; D011485:Protein Binding / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics; D064067:Rho Guanine Nucleotide Exchange Factors; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013917:Thrombin / Q000494:pharmacology; D014162:Transfection; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000099149:Ezrin
D001920:Bradykinin; D003598:Cytoskeletal Proteins; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D020662:Guanine Nucleotide Exchange Factors; D048031:JNK Mitogen-Activated Protein Kinases; D008246:Lysophospholipids; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D064067:Rho Guanine Nucleotide Exchange Factors; D013917:Thrombin; D020764:cdc42 GTP-Binding Protein; D048051:p38 Mitogen-Activated Protein Kinases; D020742:rhoA GTP-Binding Protein; D000099149:Ezrin; C512843:Mcf2 protein, mouse; C032881:lysophosphatidic acid