14-3-3 Proteins Interact with Specific MEK Kinases

Fanger, Gary R.; Widmann, Christian; Porter, Amy C.; Sather, Sue; Johnson, Gary L.; Vaillancourt, Richard

doi:10.1074/jbc.273.6.3476

Cited by 141 publications

(92 citation statements)

References 45 publications

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“…As shown, L40 cells carrying plasmids LexA-MEKK3 and GAD-mPRK2(aa 479 -670) were not able to grow on SCϪHis ϩ 3 mM 3-AT plates, even after incubation for over 1 week (data not shown). In comparison, cells with LexA-MEKK3 plus VAD-14-3-3⑀ showed robust growth on the same minimal plates and strong ␤-gal activity, consistent with our previous report that MEKK3 binds 14-3-3⑀ protein (37). This indicates that LexA-MEKK3 was expressed and nucleus-localized, and the failure of GADmPRK2(aa 479 -670) to transactivate the reporter genes was due to its inability to bind MEKK3.…”

Section: Mekk2supporting

confidence: 89%

MEK Kinase 2 Binds and Activates Protein Kinase C-related Kinase 2

Sun¹,

Vincent²,

Settleman³

et al. 2000

Journal of Biological Chemistry

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MEK kinase 2 (MEKK2) is a 70-kDa protein serine/ threonine kinase that has been shown to function as a mitogen-activated protein kinase (MAPK) kinase kinase. MEKK2 has its kinase domain in the COOH-terminal moiety of the protein. The NH 2 -terminal moiety of MEKK2 has no signature motif that would suggest a defined regulatory function. Yeast two-hybrid screening was performed to identify proteins that bind MEKK2. Protein kinase C-related kinase 2 (PRK2) was found to bind MEKK2; PRK2 has been previously shown to bind RhoA and the Src homology 3 domain of Nck. PRK2 did not bind MEKK3, which is closely related to MEKK2. The MEKK2 binding site maps to amino acids 637-660 in PRK2, which is distinct from the binding sites for RhoA and Nck. This sequence is divergent in the closely related kinase PRK1, which did not bind MEKK2. In cells, MEKK2 and PRK2 are co-immunoprecipitated and PRK2 is activated by MEKK2. Similarly, purified recombinant MEKK2 activated PRK2 in vitro. MEKK2 activation of PRK2 is independent of MEKK2 regulation of the c-Jun NH 2 -terminal kinase pathway. MEKK2 activation of PRK2 results in a bifurcation of signaling for the dual control of MAPK pathways and PRK2 regulated responses. Mitogen-activated protein kinases (MAPKs)1 are components of a three kinase module that also includes a MAPK kinase and MAPK kinase kinase (1). MEKK2 is a MAPK kinase kinase that we have shown is activated in response to several extracellular stimuli including antigen receptors in T cells and mast cells and growth factors such as epidermal growth factor and Kit ligand (stem cell factor) (2, 3). We recently demonstrated that MEKK2 translocates to the cytoplasmic face of the contact site of T cells interacting with an antigen loaded presenting cell (3). MEKK2 but not MEKK1 or MEKK3 is translocated to the T cell interface with the antigen presenting cell. MEKK2 is translocated and activated within seconds of exposure of T cells to antigen presentation. MEKK2 activation was required for its translocation because kinase-inactive MEKK2 was not recruited to the contact between the T cell and antigen presenting cell. In this system, MEKK2 signaling was found to be required for maintenance of the conjugate formation between T cell and antigen presenting cell. Although poorly defined, the activation of MEKK2 seems to involve more than one pathway. For example antigen receptor activation of MEKK2 is inhibited by wortmannin, indicating the activation of phosphatidylinositol 3-kinase is required. In contrast, epidermal growth factor stimulation of MEKK2 in COS-7 cells is insensitive to wortmannin.MEKK2 is a 70-kDa serine-threonine kinase that has its kinase domain in the COOH-terminal half of the protein (4). Analysis of the NH 2 -terminal moiety of MEKK2 does not reveal an identifiable motif that has been defined in other proteins that are known to regulate protein-protein (i.e. SH3, prolinerich, etc.) or protein-lipid (i.e. pleckstrin homology domains) interactions. Thus, the sequence of MEKK2 does not readily allow predictions of i...

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Section: Mekk2supporting

confidence: 89%

MEK Kinase 2 Binds and Activates Protein Kinase C-related Kinase 2

Sun¹,

Vincent²,

Settleman³

et al. 2000

Journal of Biological Chemistry

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“…This interaction is suppressed by a phosphorylated Raf peptide but not by its non-phosphorylated counterpart. Genetic strategies have provided strong evidence that 14-3-3 proteins, via homo-and hetero-dimeric complexes, serve as scaffolds that facilitate interactions among molecular components of signaling cascades (43,51,53). The present findings suggest that 14-3-3 proteins may play a similar role in linking G protein-coupled receptors to diverse signaling pathways by coordinating these interactions in the receptor microenvironment.…”

Section: Discussionmentioning

confidence: 55%

“…The bold type represents the peptide sequence obtained from the purified preparation of 3i loop interacting proteins, and the gray boxes indicate where this sequence is homologous to 14-3-3. development (51). It has been postulated that interaction of signaling molecules with 14-3-3 homo-or heterodimers serves as a scaffolding mechanism to facilitate interactions among molecular components of signaling cascades (42,53).…”

Section: Discussionmentioning

confidence: 99%

The ζ Isoform of 14-3-3 Proteins Interacts with the Third Intracellular Loop of Different α2-Adrenergic Receptor Subtypes

Prézeau¹,

Richman²,

Edwards

et al. 1999

Journal of Biological Chemistry

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The ␣ 2 -adrenergic receptors (␣ 2 ARs) are localized to and function on the basolateral surface in polarized renal epithelial cells via a mechanism involving the third cytoplasmic loop. 35 S]Met-14-3-3 binds to all three native ␣ 2 AR subtypes, assessed using a solid phase binding assay (␣ 2A >␣ 2B > ␣ 2C ), and this binding depends on the presence of the 3i loops. Attenuation of the ␣ 2 AR-14-3-3 interactions in the presence of a phosphorylated Raf-1 peptide corresponding to its 14-3-3 interacting domain (residues 251-266), but not by its non-phosphorylated counterpart, provides evidence for the functional specificity of these interactions and suggests one potential interface for the ␣ 2 AR and 14-3-3 interactions. These studies represent the first evidence for G protein-coupled receptor interactions with 14-3-3 proteins and may provide a mechanism for receptor localization and/or coordination of signal transduction.The three ␣ 2 -adrenergic receptor (␣ 2 AR) 1 subtypes, encoded by distinct genes (1), all couple via the G i /G o family of GTPbinding proteins to inhibition of adenylyl cyclase, suppression of voltage-sensitive calcium channels, and activation of receptor-operated potassium channels (2). These receptors also couple to activation of Ras (3, 4), the mitogen-activated protein kinase cascade (3, 5-7), and to activation of phospholipase D (8, 9).Despite the qualitatively similar signaling properties of the three ␣ 2 AR subtypes, differences in trafficking of these receptors have been reported. For example, subtype-selective differences in agonist-elicited ␣ 2 AR redistribution occur (10 -15). In addition, selective itineraries for the ␣ 2 AR subtypes are observed in polarized Madin-Darby canine kidney (MDCKII) renal epithelial cells. Thus, the ␣ 2A AR subtype is targeted directly to the basolateral surface (16), whereas the ␣ 2B AR subtype is delivered randomly to both the apical and basolateral surfaces but is rapidly lost from the apical (t1 ⁄2 ϭ 5-15 min) and selectively retained on the basolateral (t1 ⁄2 ϭ 10 -12 h) surface (17). These findings suggest that there is a molecular mechanism responsible for the selective retention of the ␣ 2B AR on the basolateral domain of MDCK cells that may be shared by all three ␣ 2 AR subtypes, as they manifest comparable halflives on that surface (17).Receptor retention on the lateral subdomain of MDCKII cells likely involves the third intracellular loop of the ␣ 2A AR, since deletion of this loop, creating the mutant ␣ 2A ⌬3iAR, results in accelerated basolateral turnover (t1 ⁄2 Х 4.5 h) when compared with that for the wild-type receptor or with ␣ 2A AR structures that have been mutated in the N terminus or the C-terminal tail (all possessing a t1 ⁄2 of 10 -12 h) (18). The accelerated turnover of the ␣ 2A ⌬3iAR when compared with the wild-type ␣ 2A AR structure suggests that the third intracellular loop interacts with proteins that either tether ␣ 2A AR to a particular surface domain or, alternatively, mask the ␣ 2A AR from interacting with endocytosis machiner...

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“…In addition, the ®ndings that MAPKK and MAPK exist as a high molecular weight complex in Xenopus oocyte (Matsuda et al, 1993) lend credence to the view that a sca olding protein may be present to physically integrate the MKK1/2-ERK1/2 modules of the higher eukaryotes. Interestingly, 14-3-3 family of proteins that interact with Rafs and MEKKs appear to be a prospective candidate for this role in mammalian cells (Fanger et al, 1998). However, this does not rule out the presence of other proteins that may be involved in this process.…”

Section: Map Kinase Kinase-1 and Map Kinase Kinase-2mentioning

confidence: 99%

Signaling by dual specificity kinases

1998

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Dual speci®city kinases that phosphorylate the Thr-and Tyr-residues within the TXY motif of MAP-kinases of play a central role in the regulation of various processes of cell growth. These dual speci®city kinases also known as MAP kinase kinases are constituents of the sequential kinase signaling modules. Seven distinct mammalian MAP kinases kinases have been identi®ed. Some of the unique signaling properties of these kinases are discussed here.

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14-3-3 Proteins Interact with Specific MEK Kinases

Cited by 141 publications

References 45 publications

MEK Kinase 2 Binds and Activates Protein Kinase C-related Kinase 2

MEK Kinase 2 Binds and Activates Protein Kinase C-related Kinase 2

The ζ Isoform of 14-3-3 Proteins Interacts with the Third Intracellular Loop of Different α2-Adrenergic Receptor Subtypes

Signaling by dual specificity kinases

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