PMID- 9707409 OWN - NLM STAT- MEDLINE DCOM- 19981009 LR - 20220318 IS - 0960-9822 (Print) IS - 0960-9822 (Linking) VI - 8 IP - 16 DP - 1998 Jul 30-Aug 13 TI - The exchange factor Ras-GRF2 activates Ras-dependent and Rac-dependent mitogen-activated protein kinase pathways. PG - 935-8 AB - Ras and Rac are membrane-associated GTPases that function as molecular switches activating intracellular mitogen-activated protein kinase (MAPK) cascades and other effector pathways in response to extracellular signals [1]. Activation of Ras and Rac into their GTP-bound conformations is directly controlled by specific guanine-nucleotide exchange factors (GEFs), which catalyze GDP release. Several Ras-specific GEFs that are related to the budding yeast protein Cdc25p have been described, whereas GEFs for Rac-related GTPases contain a region that is homologous to the oncoprotein DbI [2-3]. The Ras-GRF1 and Ras-GRF2 proteins, which couple Ras activation to serpentine receptors and calcium signals, contain both Cdc25 and DbI homology (DH) regions [3-4]. Here, we demonstrate that Ras-GRF2 is a bifunctional signaling protein that is able to bind and activate Ras and Rac, and thereby coordinate the activation of the extracellular-signal-regulated kinase (ERK) and stress-activated protein kinase (SAPK) pathways. FAU - Fan, W T AU - Fan WT AD - Banting and Best Department of Medical Research Department of Molecular and Medical Genetics University of Toronto Charles H. Best Institute 112 College Street, Toronto, M5G 1L6, Canada. FAU - Koch, C A AU - Koch CA FAU - de Hoog, C L AU - de Hoog CL FAU - Fam, N P AU - Fam NP FAU - Moran, M F AU - Moran MF LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Curr Biol JT - Current biology : CB JID - 9107782 RN - 0 (Cell Cycle Proteins) RN - 0 (Guanine Nucleotide Exchange Factors) RN - 0 (Proteins) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Recombinant Proteins) RN - 0 (ras Guanine Nucleotide Exchange Factors) RN - 0 (ras-GRF1) RN - 56092-81-0 (Ionomycin) RN - 6C74YM2NGI (Anisomycin) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 3.1.3.16 (Phosphoprotein Phosphatases) RN - EC 3.6.1.- (GTP Phosphohydrolases) RN - EC 3.6.1.- (GTP-Binding Proteins) RN - EC 3.6.5.2 (rac GTP-Binding Proteins) RN - EC 3.6.5.2 (ras Proteins) SB - IM MH - Anisomycin/pharmacology MH - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism MH - Cell Cycle Proteins/metabolism MH - Cell Line MH - Enzyme Activation MH - GTP Phosphohydrolases/*metabolism MH - GTP-Binding Proteins/*metabolism MH - Guanine Nucleotide Exchange Factors MH - Humans MH - Ionomycin/pharmacology MH - Mitogen-Activated Protein Kinase 3 MH - *Mitogen-Activated Protein Kinases MH - Phosphoprotein Phosphatases/metabolism MH - Proteins/*metabolism MH - Recombinant Fusion Proteins/metabolism MH - Recombinant Proteins/metabolism MH - Signal Transduction MH - Transfection MH - rac GTP-Binding Proteins MH - ras Guanine Nucleotide Exchange Factors MH - ras Proteins/*metabolism MH - ras-GRF1 EDAT- 1998/08/26 00:00 MHDA- 1998/08/26 00:01 CRDT- 1998/08/26 00:00 PHST- 1998/08/26 00:00 [pubmed] PHST- 1998/08/26 00:01 [medline] PHST- 1998/08/26 00:00 [entrez] AID - S0960-9822(07)00376-4 [pii] AID - 10.1016/s0960-9822(07)00376-4 [doi] PST - ppublish SO - Curr Biol. 1998 Jul 30-Aug 13;8(16):935-8. doi: 10.1016/s0960-9822(07)00376-4.