| Standard name |
BIOCARTA_SPRY_PATHWAY |
| Systematic name |
M1389 |
| Brief description |
Sprouty regulation of tyrosine kinase signals |
| Full description or abstract |
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. |
| Collection |
C2: curated gene sets CP: canonical pathways CP:BIOCARTA: BioCarta gene sets |
| Source publication |
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| Exact source |
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| Related gene sets |
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| External links |
http://www.biocarta.com/pathfiles/h_spryPathway.asp http://www.biocarta.com/pathfiles/PathwayProteinList.asp?showPFID=506 |
| Organism |
Homo sapiens |
| Contributed by |
BioCarta |
| Source platform |
EntrezGeneIds |
| Dataset references |
|
| Download gene set |
format: grp | text | gmt | gmx | xml |
Compute overlaps  |
C1: positional gene sets
C2: curated gene sets
CGP: chemical and genetic perturbations
CP: canonical pathways
CP:BIOCARTA: BioCarta gene sets
CP:KEGG: KEGG gene sets
CP:REACTOME: Reactome gene sets
C3: motif gene sets
MIR: microRNA targets
TFT: transcription factor targets
C4: computational gene sets
CGN: cancer gene neighborhoods
CM: cancer modules
C5: GO gene sets
BP: GO biological process
CC: GO cellular component
MF: GO molecular function
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Compendia expression profiles  |
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
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| Advanced query |
Further investigate
these 18 genes |
Gene families  |
Categorize these
18 genes by gene family |
| Show members |
(show 18 members mapped to 18 genes)
Original Member |
Gene Symbol |
Gene Description |
Entrez Gene Id |
| 10251 |
SPRY3 |
sprouty homolog 3 (Drosophila) |
10251 |
| 10252 |
SPRY1 |
sprouty homolog 1, antagonist of FGF signaling... |
10252 |
| 10253 |
SPRY2 |
sprouty homolog 2 (Drosophila) |
10253 |
| 1950 |
EGF |
epidermal growth factor (beta-urogastrone) |
1950 |
| 1956 |
EGFR |
epidermal growth factor receptor (erythroblast... |
1956 |
| 2885 |
GRB2 |
growth factor receptor-bound protein 2 |
2885 |
| 3265 |
HRAS |
v-Ha-ras Harvey rat sarcoma viral oncogene hom... |
3265 |
| 5594 |
MAPK1 |
mitogen-activated protein kinase 1 |
5594 |
| 5595 |
MAPK3 |
mitogen-activated protein kinase 3 |
5595 |
| 5604 |
MAP2K1 |
mitogen-activated protein kinase kinase 1 |
5604 |
| 5787 |
PTPRB |
protein tyrosine phosphatase, receptor type, B |
5787 |
| 5894 |
RAF1 |
v-raf-1 murine leukemia viral oncogene homolog 1 |
5894 |
| 5921 |
RASA1 |
RAS p21 protein activator (GTPase activating p... |
5921 |
| 6464 |
SHC1 |
SHC (Src homology 2 domain containing) transfo... |
6464 |
| 6654 |
SOS1 |
son of sevenless homolog 1 (Drosophila) |
6654 |
| 6714 |
SRC |
v-src sarcoma (Schmidt-Ruppin A-2) viral oncog... |
6714 |
| 81848 |
SPRY4 |
sprouty homolog 4 (Drosophila) |
81848 |
| 867 |
CBL |
Cas-Br-M (murine) ecotropic retroviral transfo... |
867 |
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| Version history |
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