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245	1	0	_aMitogen-activated protein kinase (MAPK)-docking sites in MAPK kinases function as tethers that are crucial for MAPK regulation in vivo
490	0		_vCellular Signalling, 18(1), p.123-134, 2006
520	3		_aDocking sites on targets of mitogen-activated protein kinases (MAPKs)facilitate accurate and efficient substrate phosphorylation. MAPK/ ERK kinases (MEKs, or MKKs), the upstream regulators of MAPKs, also contain N-terminal MAPK-docking sites, or FD-sites_; however, the in vivo functions of MEK D-sites are incompletely understood. Here we found that the ability of constitutively-active human MEK1 and MEK2 to stimulate ERK phosphorylation and to induce the neoplastic transformation of NIH 3T3 cells required the integrity of the D-site. In addition, D-site mutants of otherwise wild-type MEK1/2 were unable to anchor unphosphorylated ERK2 in the cytoplasm. ERK activation, cytoplasmic anchoring and release were completely retained in Fswap_ mutants in which MEK2's D-site was replaced with the D-site of MEK1 or yeast Ste7. Furthermore, these abilities were significantly retained when MEK2's D-site was moved to its C-terminus, or replaced by an unrelated MAPK-binding domain taken from the Ets-1 transcription factor. We conclude that the D-sites in MEKs are crucial for the activation of their cognate MAPKs in vivo, and that their primary function is to tether their cognate MAPKs near the MEK's kinase domain. This proximity effect is sufficient to explain the contribution that the D-site interaction makes to several biologically important signaling events
650	1	4	_aMITOGEN-ACTIVATED PROTEIN KINASES
650	1	4	_aSIGNAL TRANSDUCTION
650	1	4	_aPHOSPHORYLATION
650	1	4	_aBINDING SITES
650	1	4	_aPROTEIN BINDING
700	1	2	_aGrewal, S.
700	1	2	_aMolina, D.M.
700	1	2	_aBardwell, L.
856	4	0	_uhttps://drive.google.com/file/d/18pmwQ_x38R8ZMAuEO-PhvLltpK1LcesO/view?usp=drivesdk _zPara ver el documento ingresa a Google con tu cuenta: @cicy.edu.mx
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