TAILIEUCHUNG - Báo cáo khoa học: Integrating signals between cAMP and the RAS/RAF/MEK/ERK signalling pathways Based on The Anniversary Prize of the Gesellschaft fu¨r Biochemie und Molekularbiologie Lecture delivered on 5 July 2003 at the Special FEBS Meeting in Brussels

One of the hallmarks of cAMP is its ability to inhibit proliferation in many cell types, but stimulate proliferation in others. Clearly cAMP has cell type specific effects and the outcome on proliferation is largely attributed to crosstalk from cAMP to the RAS⁄RAF⁄mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) kinase (MEK)/ ERK pathway. We review the crosstalk between these two ancient and con-served pathways, describing the molecular mechanisms underlying the interactions between these pathways and discussing their possible biological importance | ềFEBS Journal REVIEW ARTICLE Integrating signals between cAMP and the RAS RAF MeK ERK signalling pathways Based on The Anniversary Prize of the Gesellschaft fur Biochemie und Molekularbiologie Lecture delivered on 5 July 2003 at the Special FEBS Meeting in Brussels Nicolas Dumaz and Richard Marais SignalTransduction Team Cancer Research UK Centre for Celland Molecular Biology The Institute of Cancer Research London UK Keywords caMp C-RAF B-RAF ERK PKA crosstalk Correspondence R. Marais SignalTransduction Laboratory Cancer Research UK Centre for Cell and Molecular Biology Institute of Cancer Research 237 Fulham Road London SW3 6JB UK Received 23 March 2005 revised 28 April 2005 accepted 12 May 2005 doi One of the hallmarks of cAMP is its ability to inhibit proliferation in many cell types but stimulate proliferation in others. Clearly cAMP has cell type specific effects and the outcome on proliferation is largely attributed to crosstalk from cAMP to the RAS RAF mitogen-activated protein kinase MAPK and extracellular signal-regulated kinase ERK kinase MEK ERK pathway. We review the crosstalk between these two ancient and conserved pathways describing the molecular mechanisms underlying the interactions between these pathways and discussing their possible biological importance. Introduction The mechanism by which cells monitor their environment has been the subject of intense scrutiny particularly over the latter half of the last century. Cells are constantly exposed to hormones growth factors cytokines physical interactions with neighbouring cells and also to chemical and physical stresses. Many of these signals activate membrane bound receptors which then activate signalling cascades that stimulate metabolic genetic and physical changes allowing cells to mount specific responses to changing environmental conditions. Signalling through these pathways can alter cell fate decisions so it must be carefully controlled to maintain normal .

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