Preferred Label : MAP Kinase Downregulation Pathway;
NCIt related terms : Phosphorylation of MEK1 by cdk5/p35 down regulates the MAP kinase pathway;
Alternative definition : BIOCARTA: Map kinases transduce responses to extracellular signals by a variety of
routes, and communicate with other pathways through extensive crosstalk networks.
A closely studied Map kinase cascade originates with tyrosine kinase activation, and
activation of Ras. Ras activates Raf, Raf activates the Map kinase kinases Mek1 and
Mek2 and these kinases activate downstream Map kinases like Erk1 and Erk2. Erk1 and
Erk2 in turn activate transgenes like p35 through the Map kinase activated transcription
factor EGR-1. Mek1 plays a central role in many different Map kinase pathways. Factors
that activate Mek1 include growth factors like NGF, cytokines, chemokines, and phorbol
ester, resulting in cellular proliferation and survival. Mek1 activation may also
play a role in differentiation in neuronal tissues. In cultured neuronal PC-12 cells,
NGF induces neurite outgrowth via Mek1 and the map kinase pathway. Constitutive activation
of Mek1 can transform cells and may play a role in cancer. The crucial role of Mek1
in a variety of pathways including cellular transformation suggests that the cell
must tightly regulate its activity. Cdk5 is a kinase that regulates the activity of
Mek1. Although Cdk5 is a member of the cyclin-dependent kinase gene family, the activity
of Cdk5 does not appear to be regulated by cyclins, but is activated by association
with p35. Cdk5 does not act as a checkpoint kinase to regulate cell cycle progression,
but acts as a regulatory kinase involved in other post-mitotic processes such as neuronal
activity such as neuronal migration during development and neurite outgrowth. Mice
lacking Cdk5 exhibit defects in neuronal development. One target of Cdk5 is Mek1.
Phosphorylation of Mek1 by Cdk5 represses Mek1 activity and blocks downstream cellular
responses. The activation of p35 by Map kinase pathways followed by deactivation of
Map kinase signaling by the Cdk5/p35 complex completes the loop of a feedback circuit
to terminate Map kinase signaling. (This definition may be outdated - see the DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_cdk5Pathway;
Origin ID : C39022;
UMLS CUI : C1518105;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
