Calpain-2 Cell Motility Pathway

Preferred Label : Calpain-2 Cell Motility Pathway;

NCIt synonyms : M-Calpain Cell Motility Pathway; Calpain Cell Motility Pathway;

NCIt related terms : mCalpain and friends in Cell motility;

Alternative definition : BIOCARTA: The mammalian calpain gene family currently contains 13 distinct large subunit products most of which complex with one of two smaller 30kDa subunits. One of the most carefully studied functions of the calpains is the regulation of integrin-mediated cell migration. Calpains digest the links between the actin cytoskeleton and several focal adhesion complex proteins; talin, paxillin and focal adhesion kinase. The release from the focal adhesion complex facilitates migration. Calpastatin is an inhibitor expressed in most cells. Calpastatin binds the four inhibitory domains of calpain. Release from calpastatin does not activate calpain. Activation requires additional signaling, coactivators, and an appropriate calcium concentration. During cell migration calpain1 (mu-calpain) acts at the leading edge as a response to integrin signals or calcium fluctuations due to the stretch activated calcium channels. Calpain1 cleaves the target proteins, talin, ezrin, paxillin, and the cytoplasmic tail of the integrins B1(a) and B3(b) to release the adhesion and form new adhesions. Calpain2 (M-calpain) is believed to be membrane bound and functions at the trailing edge of the migrating cell to cleave the integrins in response to growth factor receptor signals. PKA functions to down regulate or inhibit calpain2. In Alzheimer's disease, amyloid peptides interfere with calpain activity causing a mislocalization of cdk5. Deregulated cdk5 hyperphosphorylates tau promoting cell death in neurons. Mutations in the muscle specific calpain p94 lead to Limb Girdle muscular dystrophy 2A (LGMD2A). Over activity of calpains due to elevated calcium leads to tissue damage in the heart and brain. (This definition may be outdated - see the DesignNote.);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 Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate.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_mCalpainPathway;

Details

Origin ID

C39147;

UMLS CUI

C1516153;

Semantic type(s)
- Cell Function [UMLS semantic type]
has_gene_product_element
- C-X-C Chemokine Receptor Type 3 [NCIt concept]
- Calpain-1 Catalytic Subunit [NCIt concept]
- Calpain-2 Catalytic Subunit [NCIt concept]
- Dual Specificity Mitogen-Activated Protein Kinase Kinase 2 [NCIt concept]
- Epidermal Growth Factor [NCIt concept]
- Epidermal Growth Factor Receptor [NCIt concept]
- Focal Adhesion Kinase 1 [NCIt concept]
- GTPase HRas [NCIt concept]
- Myosin Light Chain Kinase, Smooth Muscle [NCIt concept]
- Paxillin [NCIt concept]
- Ras-Related C3 Botulinum Toxin Substrate 1 [NCIt concept]
- Son of Sevenless Homolog 1 [NCIt concept]
- cAMP-Dependent Protein Kinase Catalytic Subunit Beta [NCIt concept]
- cAMP-Dependent Protein Kinase Catalytic Subunit Gamma [NCIt concept]
- cAMP-Dependent Protein Kinase Type I-Alpha Regulatory Subunit [NCIt concept]
- cAMP-Dependent Protein Kinase Type II-Alpha Regulatory Subunit [NCIt concept]
pathway_has_gene_element
- CAPN1 wt Allele [NCIt concept]
- CAPN2 wt Allele [NCIt concept]
- CXCR3 wt Allele [NCIt concept]
- EGF wt Allele [NCIt concept]
- EGFR wt Allele [NCIt concept]
- HRAS wt Allele [NCIt concept]
- MAP2K2 wt Allele [NCIt concept]
- MYLK wt Allele [NCIt concept]
- PRKACB wt Allele [NCIt concept]
- PRKACG wt Allele [NCIt concept]
- PRKAR1A wt Allele [NCIt concept]
- PRKAR2A wt Allele [NCIt concept]
- PTK2 wt Allele [NCIt concept]
- PXN wt Allele [NCIt concept]
- RAC1 wt Allele [NCIt concept]
- SOS1 wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

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