scholarly journals Involvement of Activation of Mitogen-Activated Protein Kinase (MAPK)/Extracellular Signal-Regulated Kinase (ERK) Signaling Pathway in Proliferation of Urethral Plate Fibroblasts in Finasteride-Induced Rat Hypospadias

2018 ◽  
Vol 24 ◽  
pp. 8984-8992 ◽  
Author(s):  
Nini An ◽  
Jinpu Peng ◽  
Guoqing He ◽  
Xia Fan ◽  
Fei Li ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Erk Signaling ◽  
Urethral Plate ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

scholarly journals Rac-PAK Signaling Stimulates Extracellular Signal-Regulated Kinase (ERK) Activation by Regulating Formation of MEK1-ERK Complexes

2002 ◽  
Vol 22 (17) ◽  
pp. 6023-6033 ◽  
Author(s):  
Scott T. Eblen ◽  
Jill K. Slack ◽  
Michael J. Weber ◽  
Andrew D. Catling
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Dominant Negative ◽  
Mitogen Activated Protein Kinase ◽  
Wild Type ◽  
Erk Activation ◽  
Extracellular Signal Regulated Kinase ◽  
Signaling Complex ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

ABSTRACT Utilizing mutants of extracellular signal-regulated kinase 2 (ERK2) that are defective for intrinsic mitogen-activated protein kinase or ERK kinase (MEK) binding, we have identified a convergent signaling pathway that facilitates regulated MEK-ERK association and ERK activation. ERK2-Δ19-25 mutants defective in MEK binding could be phosphorylated in response to mitogens; however, signaling from the Raf-MEK pathway alone was insufficient to stimulate their phosphorylation in COS-1 cells. Phosphorylation of ERK2-Δ19-25 but not of wild-type ERK2 in response to Ras V12 was greatly inhibited by dominant-negative Rac. Activated forms of Rac and Cdc42 could enhance the association of wild-type ERK2 with MEK1 but not with MEK2 in serum-starved adherent cells. This effect was p21-activated kinase (PAK) dependent and required the putative PAK phosphorylation sites T292 and S298 of MEK1. In detached cells placed in suspension, ERK2 was complexed with MEK2 but not with MEK1. However, upon replating of cells onto a fibronectin matrix, there was a substantial induction of MEK1-ERK2 association and ERK activation, both of which could be inhibited by dominant-negative PAK1. These data show that Rac facilitates the assembly of a mitogen-activated protein kinase signaling complex required for ERK activation and that this facilitative signaling pathway is active during adhesion to the extracellular matrix. These findings reveal a novel mechanism by which adhesion and growth factor signals are integrated during ERK activation.

scholarly journals A Novel Mitogen-Activated Protein Kinase Docking Site in the N Terminus of MEK5α Organizes the Components of the Extracellular Signal-Regulated Kinase 5 Signaling Pathway

2005 ◽  
Vol 25 (22) ◽  
pp. 9820-9828 ◽  
Author(s):  
Jan Seyfried ◽  
Xin Wang ◽  
Giorgi Kharebava ◽  
Cathy Tournier
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Docking Site ◽  
Cellular Survival ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
N Terminus ◽  
Mitogen Activated Protein ◽  
Mapk Kinases

ABSTRACT The alternative splicing of the mek5 gene gives rise to two isoforms. MEK5β lacks an extended N terminus present in MEK5α. Comparison of their activities led us to identify a novel mitogen-activated protein kinase (MAPK) docking site in the N terminus of MEK5α that is distinct from the consensus motif identified in the other MAPK kinases. It consists of a cluster of acidic residues at position 61 and positions 63 to 66. The formation of the MEK5/extracellular signal-regulated kinase 5 (ERK5) complex is critical for MEK5 to activate ERK5, to increase transcription via MEF2, and to enhance cellular survival in response to osmotic stress. Certain mutations in the ERK5 docking site that prevent MEK5/ERK5 interaction also abrogate the ability of MEKK2 to bind and activate MEK5. However, the identification of MEK5α mutants with selective binding defect demonstrates that the MEK5/ERK5 interaction does not rely on the binding of MEK5α to MEKK2 via their respective PB1 domains. Altogether these results establish that the N terminus of MEK5α is critical for the specific organization of the components of the ERK5 signaling pathway.

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