We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
The ras-related GTPase rac1 regulates a proliferative pathway selectively utilized by G-protein coupled receptors.
- Authors
Burstein, Ethan S; Hesterberg, Diane J; Gutkind, J Silvio; Brann, Mark R; Currier, Erika A; Messier, Terri L
- Abstract
Ras and rac are each members of the superfamily of monomeric GTPases and both function as molecular switches to link cell-surface signals to intracellular responses. Using a novel assay of cellular proliferation called R-SATTM (Receptor Selection and Amplification Technology), we examined the roles of ras and rac in mediating the proliferative responses to a variety of cell-surface receptors. Activated, wild-type and dominant-negative mutants of rac and ras were tested for their effects on cellular proliferation either alone or in combination with receptors. Activated rac (rac Q61L, henceforth rac*) and ras (ras G12V, henceforth ras*) each induced strong proliferative responses. Dominant-negative rac (rac T17N, henceforth rac(-)) dramatically suppressed proliferative responses to G-protein coupled receptors (GPCR's) including the m5 muscarinic receptor and the α1B adrenergic receptor. In contrast, rac(-) had little or no effect upon responses to the tyrosine kinase receptor TrkC, and only partially suppressed responses to the Janus kinase (JAK/STAT) linked granulocyte macrophage colony stimulating factor (GM-CSF) receptor. Dominant-negative ras (ras T17N, henceforth ras(-)) blocked the proliferative responses to all of the tested receptors. Compared to rac(-) and ras(-), wild-type rac and ras had only modest effects on the tested receptors. Overall these results demonstrate that rac mediates the proliferative effects of G-protein coupled receptors through a pathway that is distinct from the proliferative signaling pathway utilized by tyrosine kinase linked and JAK-linked receptors.
- Subjects
G proteins; RAS oncogenes; PROTEIN-tyrosine kinases; CELL proliferation
- Publication
Oncogene, 1998, Vol 17, Issue 12, p1617
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1202067