Sprouty Regulation of Tyrosine Kinase Signaling Pathway

Preferred Label : Sprouty Regulation of Tyrosine Kinase Signaling Pathway;

NCIt related terms : Sprouty regulation of tyrosine kinase signals;

Alternative definition : BIOCARTA: Four different members of the Sprouty protein family block the cellular proliferation and differentiation induced by several different growth factors, including EGF and FGF. One mechanism by which Sprouty proteins inhibit signaling is through binding to Grb-2, a signaling intermediary between the tyrosine kinase growth factors and the Ras/map kinase pathway. Binding of Sprouty to Grb-2 prevents Grb-2 and Sos-1 from interacting with downstream signaling factors that activate Ras and map kinases, including Ras, Raf-1, Mek1, Erk1/2, and downstream transcription factors. The action of Sprouty as an inhibitor of this pathway requires Sprouty phosphorylation and membrane localization at the site of the factors it interacts with. The inhibition of growth factor signaling by Sprouty is specific to the Ras pathway since the PI3 Kinase pathway responsible for cell survival signals from growth factor receptors is not inhibited by Sprouty. Tyrosine kinase activity of growth factor receptors is also not affected. The mechanism by which Sprouty inhibits Ras activation may be by blocking the nucleotide exchange activity of Sos. Sprouty expression is induced by growth factor receptor activation of Ras signaling, provided a self-regulatory feedback inhibition mechanism that regulates growth factor signaling through Ras. In addition to blocking the Ras pathway, Sprouty also induces protein tyrosine phosphatase 1B activity. Activation of PTP1B by Sprouty is responsible for the inhibition of cellular migration that Sprouty causes, but is not involved in regulation of cellular proliferation. While blocking receptor tyrosine kinase signaling, at least one member of the Sprouty family, Sprouty-2, also acts by one mechanism to stimulate EGF receptor signaling. Cbl targets the EGF receptor for tagging with ubiquitin and proteolytic destruction. Sprouty-2 binds to Cbl and blocks the ubiquitination and destruction of the EGF receptor, increasing EGF 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 (This definition may be outdated - see the DesignNote.);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_spryPathway;

Details

Origin ID

C39236;

UMLS CUI

C1519482;

Semantic type(s)
- Cell Function [UMLS semantic type]
has_gene_product_element
- Dual Specificity Mitogen-Activated Protein Kinase Kinase 1 [NCIt concept]
- Dual Specificity Mitogen-Activated Protein Kinase Kinase 2 [NCIt concept]
- E3 Ubiquitin-Protein Ligase CBL [NCIt concept]
- Epidermal Growth Factor [NCIt concept]
- Epidermal Growth Factor Receptor [NCIt concept]
- GTPase HRas [NCIt concept]
- Growth Factor Receptor-Bound Protein 2 [NCIt concept]
- Mitogen-Activated Protein Kinase 1 [NCIt concept]
- Mitogen-Activated Protein Kinase 3 [NCIt concept]
- Protein Sprouty Homolog 2 [NCIt concept]
- Proto-Oncogene Tyrosine-Protein Kinase Src [NCIt concept]
- RAF Proto-Oncogene Serine/Threonine-Protein Kinase [NCIt concept]
- Ras GTPase-Activating Protein 1 [NCIt concept]
- Receptor-Type Tyrosine-Protein Phosphatase Beta [NCIt concept]
- SHC-Transforming Protein 1 [NCIt concept]
- Son of Sevenless Homolog 1 [NCIt concept]
pathway_has_gene_element
- CBL wt Allele [NCIt concept]
- EGF wt Allele [NCIt concept]
- EGFR wt Allele [NCIt concept]
- GRB2 wt Allele [NCIt concept]
- HRAS wt Allele [NCIt concept]
- MAP2K1 wt Allele [NCIt concept]
- MAP2K2 wt Allele [NCIt concept]
- MAPK1 wt Allele [NCIt concept]
- MAPK3 wt Allele [NCIt concept]
- PTPRB wt Allele [NCIt concept]
- RAF1 wt Allele [NCIt concept]
- RASA1 wt Allele [NCIt concept]
- SHC1 wt Allele [NCIt concept]
- SOS1 wt Allele [NCIt concept]
- SPRY2 wt Allele [NCIt concept]
- SRC wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

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