The Rac/Cdc42 guanine nucleotide exchange factor beta1Pix enhances mastoparan-activated Gi-dependent pathway in mast cells.
Carbachol stimulates granule exocytosis, phospholipase C (PLC), and phospholipase D (PLD) in RBL-2H3hm1 mast cells by a mechanism that involves Galphaq. However, mastoparan stimulates the same responses through Gi protein. Both Gi and Galphaq pathways are suppressed by Clostridium difficile toxin B, suggesting that Rac and Cdc42 small GTPases are also involved. Over-expression of beta1Pix, a guanine nucleotide exchange factor for Rac and Cdc42, enhances mastoparan-but not carbachol-induced hexosaminidase secretion and PLC and PLD activation. Furthermore, cells expressing beta1Pix exhibit elevated levels of mastoparan-stimulated IP3 production. Taken together, these findings implicate beta1Pix in regulating hexoasaminidase secretion and IP3 production in early stage upon mastoparan stimulation.
Chahdi
Ahmed
A
Division of Nephrology and the Cardiovascular Research Center, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA. achahdi@mcw.edu
Sorokin
Andrey
A
Dunn
Michael J
MJ
Landry
Yves
Y
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D010455:Peptides; D051381:Rats; D064067:Rho Guanine Nucleotide Exchange Factors; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014862:Wasp Venoms / Q000494:pharmacology*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D064067:Rho Guanine Nucleotide Exchange Factors; D014862:Wasp Venoms; C037500:mastoparan; D002217:Carbachol; D019204:GTP-Binding Proteins; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins