The interplay between @entity1919 ( @entity268 )-dependent protein kinase A (PKA)- and @entity11517 -mediated signaling pathways is expected to determine further loss, maintenance, or modulation of differentiation and proliferation of a particular cell. Therefore, the relationship and nature of the cross-talk between these two major signaling systems are of utmost importance to the understanding of these processes in both normal and neoplastic cells. In view of their paramount physiological importance, one would expect the existence of a well-controlled bidirectional interaction between these pathways, which would be more appropriate and in agreement with basic principles of cellular homeostasis. However, based on the discovery that activated PKA may inhibit ras-mediated translocation of @entity11956 to the plasma membrane, it is generally accepted that the cross-talk between @entity268 /PKA and @entity11517 -mediated signal transduction pathways is unilateral, i.e., that the activation of PKA regulates growth factor receptor protein @entity669 kinase-mediated signaling. To challenge the validity of a unilateral approach, we decided to test the possible existence of cross-talk of a bidirectional nature between the aforementioned signaling pathways at different stages of malignant differentiation. For that purpose, we investigated the nature of the cross-talk existing between a known receptor protein @entity669 kinase- @entity6354 receptor ( @entity12841 ) and PKA in highly metastatic and nonmetastatic cloned variants of a @entity19 @entity1492 (T-10). Our study revealed the existence of principal differences in PKA activity between metastatic and nonmetastatic cloned @entity1492 variants that may be due to the differential expression and membrane translocation of the @entity5207 ( @entity11518 ) small mass G-protein. Most importantly, our experiments have demonstrated the existence of a novel character of interactions between @entity12841 and PKA, because the ligation of the @entity12841 by @entity6354 in the metastatic variant induced a high activity of PKA. These findings are of prime importance, because they reveal the existence of a new relationship between two major signal transduction pathways in @entity1 cells, i.e., the existence of a bilateral interaction between the ras- and @entity268 /PKA-mediated signal transduction pathways. Furthermore, the fact that two @entity5 cell variants originating in the same @entity5 and differing in their metastatic capacity differ as well in the nature of the cross-talk between major signal generation systems imposes new challenges for the future use of biological response modulators to cure @entity5 and restrict metastatic spread.

@entity6354 regulates protein kinase A activity in @entity19 @entity1492 cells: differences between metastatic and nonmetastatic XXXX cell variants.

@entity268 :: ('CHEBI:17489', 'Chemical') :: ['cAMP'] @entity1 :: ('9606', 'Species') :: ['mammalian'] @entity11956 :: ('110157(Tax:10090)', 'Gene') :: ['c-Raf-1'] @entity11517 :: ('15461(Tax:10090)', 'Gene') :: ['p21ras'] @entity12841 :: ('13649(Tax:10090)', 'Gene') :: ['EGFR'] @entity19 :: ('10090', 'Species') :: ['murine'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer'] @entity11518 :: ('16653(Tax:10090)', 'Gene') :: ['Ki-ras'] @entity1492 :: ('MESH:D005354', 'Disease') :: ['fibrosarcoma'] @entity6354 :: ('13645(Tax:10090)', 'Gene') :: ['epidermal growth factor'] @entity5207 :: ('12575(Tax:10090)', 'Gene') :: ['p21'] @entity1919 :: ('MESH:D000242', 'Chemical') :: ['cyclic AMP'] @entity669 :: ('CHEBI:18186', 'Chemical') :: ['tyrosine']
@entity5 :: (MESH:D009369,Disease) :: ['tumor']
