G-proteins are involved in the signal transduction processes ranging from sensory perception to cellular growth control mechanism. The impairment of G-protein function has been implicated in several pathological conditions such as pseudohypothyroidism, cardiac dysfunction, and oncogenesis. Constitutively activated G-protein pathways have been demonstrated to cause cellular transformation. The precise mechanism by which these mutations in G-proteins disrupt normal cell growth has not been fully understood. In addition, the growing list of G-protein of subunits has left several members of this class of signal-transducers without defined receptors or effectors. G-alpha12 and G-alpha13 are the members of G 12 family of G proteins. GTPase deficient mutants of G-alpha12 and G-alpha13 readily transform the fibroblast cell lines. Previously we have shown that these alpha-subunits activate Na+/H+ exchangers and unique set of primary response genes. Our recent studies indicate that these alpha-subunits also activate the newly identified Jun N-terminal Kinase (JNK) family of Mitogen Activated Protein Kinases (MAP kinases). Specifically this proposal will focus on identifying the signaling components regulated by G-alpha12 and G-alpha13 in relation to their oncogenicity of these alpha- subunits.
The specific aims of this proposal are 1. To define the role of G-alpha12 and G-alpha13 in activating growth factor-sensitive Na+/H+ exchanger; 2. To analyze the mechanism of G-alpha12 and G-alpha13 activation of specific set of primary response genes; and 3. To analyze the mechanism of G-alpha12 and G-alpha13 activation JNK. The long term objective of this project is to identify the role of G-protein regulated signal transduction pathways in relation to cell growth and development.
| Ha, Ji Hee; Ward, Jeremy D; Varadarajalu, Lakshmi et al. (2014) The gep proto-oncogene G?12 mediates LPA-stimulated activation of CREB in ovarian cancer cells. Cell Signal 26:122-32 |
