Structural organization of MAP-kinase signaling modules by scaffold proteins in yeast and mammals.

MAP-kinase signaling pathways are activated by multiple extracellular stimuli. The specificity of activation and function of MAP-kinase signaling modules is determined, in part, by scaffold proteins that create multienzyme complexes. In Saccharomyces cerevisiae, two MAP-kinase-scaffold proteins have been identified. Recent studies of mammalian cells have also led to the identification of putative scaffold proteins. These scaffold proteins appear to facilitate MAP-kinase activation, in response to specific physiological stimuli, and to insulate the bound MAP-kinase module against activation by irrelevant stimuli. Scaffold proteins are therefore critical components of MAP-kinase modules and ensure signaling specificity.

[1]  F. Posas,et al.  Osmotic activation of the HOG MAPK pathway via Ste11p MAPKKK: scaffold role of Pbs2p MAPKK. , 1997, Science.

[2]  E. Elion,et al.  Ste5: a meeting place for MAP kinases and their associates. , 1995, Trends in cell biology.

[3]  R. Davis,et al.  Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways , 1996, Journal of Molecular Medicine.

[4]  M E Greenberg,et al.  A cytoplasmic inhibitor of the JNK signal transduction pathway. , 1997, Science.

[5]  R. Kolesnick,et al.  Kinase Suppressor of Ras Is Ceramide-Activated Protein Kinase , 1997, Cell.

[6]  B. Errede,et al.  The proliferation of MAP kinase signaling pathways in yeast. , 1995, Current opinion in cell biology.

[7]  C. Widmann,et al.  MEKKs, GCKs, MLKs, PAKs, TAKs, and tpls: upstream regulators of the c-Jun amino-terminal kinases? , 1997, Current opinion in genetics & development.

[8]  H. Schaeffer,et al.  MP1: a MEK binding partner that enhances enzymatic activation of the MAP kinase cascade. , 1998, Science.

[9]  G. Fink,et al.  The riddle of MAP kinase signaling specificity. , 1998, Trends in genetics : TIG.

[10]  David Y. Thomas,et al.  Interaction of the Grb10 Adapter Protein with the Raf1 and MEK1 Kinases* , 1998, The Journal of Biological Chemistry.

[11]  Joseph D. Schrag,et al.  Interaction of a G-protein β-subunit with a conserved sequence in Ste20/PAK family protein kinases , 1998, Nature.

[12]  W. Fantl,et al.  Regulation of the MAP kinase pathway by mammalian Ksr through direct interaction with MEK and ERK , 1998, Current Biology.

[13]  J. Yasuda,et al.  A mammalian scaffold complex that selectively mediates MAP kinase activation. , 1998, Science.

[14]  J. Downward,et al.  Murine Ksr interacts with MEK and inhibits Ras-induced transformation , 1998, Current Biology.

[15]  Jiahuai Han,et al.  NIK is a new Ste20‐related kinase that binds NCK and MEKK1 and activates the SAPK/JNK cascade via a conserved regulatory domain , 1997, The EMBO journal.

[16]  Francesc Posas,et al.  Yeast HOG1 MAP Kinase Cascade Is Regulated by a Multistep Phosphorelay Mechanism in the SLN1–YPD1–SSK1 “Two-Component” Osmosensor , 1996, Cell.

[17]  M. Cobb,et al.  MEKK1 Binds Directly to the c-Jun N-terminal Kinases/Stress-activated Protein Kinases* , 1997, The Journal of Biological Chemistry.

[18]  E. Elion,et al.  Functional binding between Gβ and the LIM domain of Ste5 is required to activate the MEKK Ste11 , 1998, Current Biology.

[19]  M. Snyder,et al.  The Spa2-related protein, Sph1p, is important for polarized growth in yeast. , 1998, Journal of cell science.

[20]  K. Clark,et al.  Pheromone Response in Yeast: Association of Bem1p with Proteins of the MAP Kinase Cascade and Actin , 1995, Science.

[21]  E. Elion,et al.  The SH3-domain protein Bem1 coordinates mitogen-activated protein kinase cascade activation with cell cycle control in Saccharomyces cerevisiae , 1996, Molecular and cellular biology.

[22]  B. Errede,et al.  Coordination of the mating and cell integrity mitogen-activated protein kinase pathways in Saccharomyces cerevisiae , 1997, Molecular and cellular biology.

[23]  E. Nishida,et al.  A novel SAPK/JNK kinase, MKK7, stimulated by TNFα and cellular stresses , 1997, The EMBO journal.

[24]  T. Pawson,et al.  Signaling through scaffold, anchoring, and adaptor proteins. , 1997, Science.

[25]  E Schaefer,et al.  The MAP kinase kinase kinase MLK2 co‐localizes with activated JNK along microtubules and associates with kinesin superfamily motor KIF3 , 1998, The EMBO journal.

[26]  M. Snyder,et al.  Spa2p Interacts with Cell Polarity Proteins and Signaling Components Involved in Yeast Cell Morphogenesis , 1998, Molecular and Cellular Biology.

[27]  P. Pryciak,et al.  Membrane recruitment of the kinase cascade scaffold protein Ste5 by the Gbetagamma complex underlies activation of the yeast pheromone response pathway. , 1998, Genes & development.

[28]  J. Thorner,et al.  Ste5 RING-H2 domain: role in Ste4-promoted oligomerization for yeast pheromone signaling. , 1997, Science.

[29]  J. Hartwig,et al.  Actin-binding protein-280 binds the stress-activated protein kinase (SAPK) activator SEK-1 and is required for tumor necrosis factor-alpha activation of SAPK in melanoma cells. , 1997, The Journal of biological chemistry.

[30]  Y. Ip,et al.  Signal transduction by the c-Jun N-terminal kinase (JNK)--from inflammation to development. , 1998, Current opinion in cell biology.

[31]  J. Downward KSR: A novel player in the RAS pathway , 1995, Cell.

[32]  G. Waeber,et al.  IB1, a JIP-1-related Nuclear Protein Present in Insulin-secreting Cells* , 1998, The Journal of Biological Chemistry.