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Mitogenic signalling pathways from G protein-coupled receptors (GPCRs) to the mitogen-activated protein kinase (MAPK) cascade may involve ?- or ??-subunits of heterotrimeric G proteins, receptor or nonreceptor tyrosine kinases, adaptor molecules, phosphoinositide 3-kinases, protein kinase C, and probably other proteins. The majority of models describing the connection of different signalling proteins within a mitogenic pathway are based on experimental data obtained by co- and overexpression of epitope-tagged MAPK together with the respective GPCR and other signalling proteins of interest in transfectable cell lines. Here the link of the bradykinin B 2  receptor (B 2 R) to MAPK in the COS-7 cell expression system is compared with mitogenic signalling pathways of bradykinin in various tumour cell lines. It becomes evident that in natural or tumour cells expressing individual amounts and different isoforms of signalling proteins completely other relations between B 2 R and MAPK may exist than in COS-7 cells, suggesting a high degree of cellular specificity in mitogenic signalling.

Bradykinin Signalling to MAP Kinase: Cell-Specific Connections versus Principle Mitogenic Pathways