scholarly journals Signalling pathway leading to an activation of mitogen-activated protein kinase by stimulating M3 muscarinic receptor

1999 ◽  
Vol 337 (2) ◽  
pp. 275-280 ◽  
Author(s):  
Jee-Young KIM ◽  
Myung-Soon YANG ◽  
Chun-Do OH ◽  
Kyong-Tai KIM ◽  
Mahn Joon HA ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Map Kinase ◽  
Muscarinic Receptor ◽  
Small Gtpase ◽  
Signalling Pathway ◽  
C Cells ◽  
Down Regulation ◽  
Human Neuroblastoma ◽  
Mitogen Activated Protein ◽  
M3 Muscarinic Receptor

The signalling pathway leading to an activation of mitogen-activated protein (MAP) kinase subtypes Erk-1 and -2 upon stimulation of muscarinic receptor with carbachol in human neuroblastoma SK-N-BE2(C) cells was investigated. Carbachol activated Erk-1/-2 by stimulating M3 muscarinic receptor, as determined by specific antagonists for individual muscarinic receptors. The activation of Erk-1/-2 by carbachol was blocked by the inhibition or down-regulation of protein kinase C (PKC). Among the multiple PKC isoforms expressed in SK-N-BE2(C) cells, only PKCε was activated by the treatment of carbachol, and selective down-regulation of PKCε was sufficient to block Erk-1/-2 activation. Carbachol treatment induced activation of the serine/threonine protein kinase Raf, and an inhibition of Raf blocked Erk-1/-2 activation. Ectopic expression of inhibitory small GTPase Ras, RasN17, blocked the carbachol-induced Raf activation without affecting the activation of PKCε, while the inhibition of PKC blocked the Raf activation. Thus, these results suggest that carbachol-induced activation of PKCε mediates Erk-1/-2 activation by a sequential activation of Ras, Raf and MAP kinase kinase.

scholarly journals Signalling pathway leading to an activation of mitogen-activated protein kinase by stimulating M3 muscarinic receptor

1999 ◽  
Vol 337 (2) ◽  
pp. 275 ◽  
Author(s):  
Jee-Young KIM ◽  
Myung-Soon YANG ◽  
Chun-Do OH ◽  
Kyong-Tai KIM ◽  
Mahn Joon HA ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Muscarinic Receptor ◽  
Signalling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
M3 Muscarinic Receptor

scholarly journals MAPK15 is part of the ULK complex and controls its activity to regulate early phases of the autophagic process

2018 ◽  
Vol 293 (41) ◽  
pp. 15962-15976 ◽  
Author(s):  
David Colecchia ◽  
Francesca Dapporto ◽  
Serena Tronnolone ◽  
Laura Salvini ◽  
Mario Chiariello
Keyword(s):  
Protein Kinase ◽  
Map Kinase ◽  
Cell Transformation ◽  
Human Diseases ◽  
Homologous Protein ◽  
Mitogen Activated Protein ◽  
Autophagic Process ◽  
Amp Activated Protein Kinase ◽  
Related Proteins ◽  
Early Phases

Autophagy, a pathway for bulk protein degradation and removal of damaged organelles, represents one of the major responses of cells to stress, thereby exerting a strict control on their correct functioning. Consequently, this process has been involved in the pathogenesis and therapeutic responses of several human diseases. Mitogen-activated protein (MAP) kinase 15 (MAPK15) is an atypical member of the MAP kinase family that recently emerged as a key modulator of autophagy and, through this, of cell transformation. Still, no information is available about signaling pathways mediating the effect of MAPK15 on this process, nor is it known which phase of autophagosome biogenesis is affected by this MAP kinase. Here, we demonstrate that MAPK15 stimulated 5′-AMP–activated protein kinase–dependent activity of UNC-51-like kinase 1 (ULK1), the only protein kinase among the ATG-related proteins, toward downstream substrates and signaling intermediates. Importantly, MAPK15 directly interacted with the ULK1 complex and mediated ULK1 activation induced by starvation, a classical stimulus for the autophagic process. In turn, ULK1 and its highly homologous protein ULK2 are able to transduce MAPK15 signals stimulating early phases of autophagosomal biogenesis in a multikinase cascade that offers numerous potential targets for future therapeutic intervention in cancer and other autophagy-related human diseases.

A yeast mitogen-activated protein kinase homolog (Mpk1p) mediates signalling by protein kinase C

1993 ◽  
Vol 13 (5) ◽  
pp. 3067-3075 ◽  
Author(s):  
K S Lee ◽  
K Irie ◽  
Y Gotoh ◽  
Y Watanabe ◽  
H Araki ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Map Kinase ◽  
Protein Kinases ◽  
Map Kinases ◽  
Pheromone Response ◽  
Pheromone Response Pathway ◽  
Kinase C ◽  
Mitogen Activated Protein ◽  
Kinase Cascade ◽  
Protein Kinase Cascade

Mitogen-activated protein (MAP) kinases are activated in response to a variety of stimuli through a protein kinase cascade that results in their phosphorylation on tyrosine and threonine residues. The molecular nature of this cascade is just beginning to emerge. Here we report the isolation of a Saccharomyces cerevisiae gene encoding a functional analog of mammalian MAP kinases, designated MPK1 (for MAP kinase). The MPK1 gene was isolated as a dosage-dependent suppressor of the cell lysis defect associated with deletion of the BCK1 gene. The BCK1 gene is also predicted to encode a protein kinase which has been proposed to function downstream of the protein kinase C isozyme encoded by PKC1. The MPK1 gene possesses a 1.5-kb uninterrupted open reading frame predicted to encode a 53-kDa protein. The predicted Mpk1 protein (Mpk1p) shares 48 to 50% sequence identity with Xenopus MAP kinase and with the yeast mating pheromone response pathway components, Fus3p and Kss1p. Deletion of MPK1 resulted in a temperature-dependent cell lysis defect that was virtually indistinguishable from that resulting from deletion of BCK1, suggesting that the protein kinases encoded by these genes function in a common pathway. Expression of Xenopus MAP kinase suppressed the defect associated with loss of MPK1 but not the mating-related defects associated with loss of FUS3 or KSS1, indicating functional conservation between the former two protein kinases. Mutation of the presumptive phosphorylated tyrosine and threonine residues of Mpk1p individually to phenylalanine and alanine, respectively, severely impaired Mpk1p function. Additional epistasis experiments, and the overall architectural similarity between the PKC1-mediated pathway and the pheromone response pathway, suggest that Pkc1p regulates a protein kinase cascade in which Bck1p activates a pair of protein kinases, designated Mkk1p and Mkk2p (for MAP kinase-kinase), which in turn activate Mpk1p.

Identification and characterization of a new mammalian mitogen-activated protein kinase kinase, MKK2

1993 ◽  
Vol 13 (8) ◽  
pp. 4539-4548
Author(s):  
J Wu ◽  
J K Harrison ◽  
P Dent ◽  
K R Lynch ◽  
M J Weber ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Map Kinase ◽  
Protein Kinases ◽  
Map Kinases ◽  
Sodium Dodecyl ◽  
Rat Tissues ◽  
Tyrosine Residues ◽  
Mitogen Activated Protein ◽  
Map Kinase Kinase

Mitogen-activated protein (MAP) kinases are serine/threonine protein kinases activated by dual phosphorylation on threonine and tyrosine residues. A MAP kinase kinase (MKK1 or MEK1) has been identified as a dual-specificity protein kinase that is sufficient to phosphorylate MAP kinases p42mapk and p44mapk on the regulatory threonine and tyrosine residues. Because of the multiplicity of MAP kinase isoforms and the diverse circumstances and agonists leading to their activation, we thought it unlikely that a single MKK could accommodate this complexity. Indeed, two protein bands with MKK activity have previously been identified after renaturation following sodium dodecyl sulfate-polyacrylamide gel electrophoresis. We now report the molecular cloning and characterization of a second rat MAP kinase kinase cDNA, MKK2. MKK2 cDNA contains an open reading frame encoding a protein of 400 amino acids, 7 residues longer than MKK1 (MEK1). The amino acid sequence of MKK2 is 81% identical to that of MKK1, but nucleotide sequence differences occur throughout the aligned MKK2 and MKK1 cDNAs, indicating that MKK2 is the product of a distinct gene. MKK1 and MKK2 mRNAs are expressed differently in rat tissues. Both cDNAs when expressed in COS cells displayed the ability to phosphorylate and activate p42mapk and p44mapk, both MKK1 and MKK2 were activated in vivo in response to serum, and both could be phosphorylated and activated by the v-Raf protein in vitro. However, differences between MKK1 and MKK2 in sites of phosphorylation by proline-directed protein kinases predict differences in feedback regulation.

MKK1 and MKK2, which encode Saccharomyces cerevisiae mitogen-activated protein kinase-kinase homologs, function in the pathway mediated by protein kinase C

1993 ◽  
Vol 13 (5) ◽  
pp. 3076-3083
Author(s):  
K Irie ◽  
M Takase ◽  
K S Lee ◽  
D E Levin ◽  
H Araki ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Map Kinase ◽  
Protein Kinases ◽  
Cell Lysis ◽  
Yeast Cells ◽  
Temperature Sensitive ◽  
Kinase C ◽  
Mitogen Activated Protein

The PKC1 gene of Saccharomyces cerevisiae encodes a homolog of mammalian protein kinase C that is required for normal growth and division of yeast cells. We report here the isolation of the yeast MKK1 and MKK2 (for mitogen-activated protein [MAP] kinase-kinase) genes which, when overexpressed, suppress the cell lysis defect of a temperature-sensitive pkc1 mutant. The MKK genes encode protein kinases most similar to the STE7 product of S. cerevisiae, the byr1 product of Schizosaccharomyces pombe, and vertebrate MAP kinase-kinases. Deletion of either MKK gene alone did not cause any apparent phenotypic defects, but deletion of both MKK1 and MKK2 resulted in a temperature-sensitive cell lysis defect that was suppressed by osmotic stabilizers. This phenotypic defect is similar to that associated with deletion of the BCK1 gene, which is thought to function in the pathway mediated by PCK1. The BCK1 gene also encodes a predicted protein kinase. Overexpression of MKK1 suppressed the growth defect caused by deletion of BCK1, whereas an activated allele of BCK1 (BCK1-20) did not suppress the defect of the mkk1 mkk2 double disruption. Furthermore, overexpression of MPK1, which encodes a protein kinase closely related to vertebrate MAP kinases, suppressed the defect of the mkk1 mkk2 double mutant. These results suggest that MKK1 and MKK2 function in a signal transduction pathway involving the protein kinases encoded by PKC1, BCK1, and MPK1. Genetic epistasis experiments indicated that the site of action for MKK1 and MKK2 is between BCK1 and MPK1.

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