Sprouty homolog 2 (Drosophila), also known as SPRY2, is a protein which in humans is encoded by the SPRY2 gene. [5]
Sprouty homolog 2 (Drosophila), also known as SPRY2, is a protein which in humans is encoded by the SPRY2 gene. [5]
This gene encodes a protein belonging to the sprouty family. The encoded protein contains a carboxyl-terminal cysteine-rich domain essential for the inhibitory activity on receptor tyrosine kinase signaling proteins and is required for growth factor stimulated translocation of the protein to membrane ruffles. In primary dermal endothelial cells this gene is transiently upregulated in response to fibroblast growth factor two. This protein is indirectly involved in the non-cell autonomous inhibitory effect on fibroblast growth factor two signaling. The protein interacts with Cas-Br-M (murine) ectropic retroviral transforming sequence, and can function as a bimodal regulator of epidermal growth factor receptor/mitogen-activated protein kinase signaling. This protein may play a role in alveoli branching during lung development as shown by a similar mouse protein. [6]
SPRY2 is a negative feedback regulator of multiple receptor tyrosine kinases (RTKs) including receptors for fibroblast growth factor (FGF), [5] epidermal growth factor (EGF), [7] and hepatocyte growth factor (HGF). [8] Antagonization of growth factor mediated pathways, cell migration, and cellular differentiation occurs through the ERK pathway. [7] Spry2 can also enhance EGFR signaling by sequestering CBL. Spry gene expression has been reported silenced or repressed in cancer of the breast, liver, lung, prostate, [7] and in lymphoma. [9] Human spry2 expression is localized to the microtubules in unstimulated cells. [10] All sprouty isoforms inhibit the ERK pathway by themselves, but can also form heterodimers and homodimers which have enhanced inhibition. [10]
SPRY2 has been shown to interact with Cbl gene. [11] [12] [13]
The epidermal growth factor receptor is a transmembrane protein that is a receptor for members of the epidermal growth factor family of extracellular protein ligands.
Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase proteins. Receptor tyrosine kinases have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Mutations in receptor tyrosine kinases lead to activation of a series of signalling cascades which have numerous effects on protein expression. Receptor tyrosine kinases are part of the larger family of protein tyrosine kinases, encompassing the receptor tyrosine kinase proteins which contain a transmembrane domain, as well as the non-receptor tyrosine kinases which do not possess transmembrane domains.
Growth factor receptor-bound protein 2, also known as Grb2, is an adaptor protein involved in signal transduction/cell communication. In humans, the GRB2 protein is encoded by the GRB2 gene.
Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) also known as protein-tyrosine phosphatase 1D (PTP-1D), Src homology region 2 domain-containing phosphatase-2 (SHP-2), or protein-tyrosine phosphatase 2C (PTP-2C) is an enzyme that in humans is encoded by the PTPN11 gene. PTPN11 is a protein tyrosine phosphatase (PTP) Shp2.
Cbl is a mammalian gene encoding the protein CBL which is an E3 ubiquitin-protein ligase involved in cell signalling and protein ubiquitination. Mutations to this gene have been implicated in a number of human cancers, particularly acute myeloid leukaemia.
Caveolin-1 is a protein that in humans is encoded by the CAV1 gene.
Tyrosine-protein kinase HCK is an enzyme that in humans is encoded by the HCK gene.
Receptor tyrosine-protein kinase erbB-4 is an enzyme that in humans is encoded by the ERBB4 gene. Alternatively spliced variants that encode different protein isoforms have been described; however, not all variants have been fully characterized.
Crk-like protein is a protein that in humans is encoded by the CRKL gene.
Phosphatidylinositol 3-kinase regulatory subunit beta is an enzyme that in humans is encoded by the PIK3R2 gene.
Rap guanine nucleotide exchange factor 1 is a protein that in humans is encoded by the RAPGEF1 gene.
CBL-B is an E3 ubiquitin-protein ligase that in humans is encoded by the CBLB gene. CBLB is a member of the CBL gene family.
Fibroblast growth factor receptor substrate 2 is a protein that in humans is encoded by the FRS2 gene.
Signal transduction protein CBL-C is a protein that in humans is encoded by the CBLC gene.
Protein sprouty homolog 1 is a protein that in humans is encoded by the SPRY1 gene.
Protein sprouty homolog 3 is a protein that in humans is encoded by the SPRY3 gene.
Sprouty-related, EVH1 domain-containing protein 1 (Spread-1) is a protein that in humans is encoded by the SPRED1 gene located on chromosome 15q13.2 and has seven coding exons.
In molecular biology, the protein Sprouty is a developmental protein involved in cell signalling. It works by inhibiting the MAPK/ERK pathway.
Sprouty-related, EVH1 domain-containing protein 3 also known as Spread-3 is a protein that in humans is encoded by the SPRED3 gene.
In molecular biology the SPR domain is a protein domain found in the Sprouty (Spry) and Spred proteins. These have been identified as inhibitors of the Ras/mitogen-activated protein kinase (MAPK) cascade, a pathway crucial for developmental processes initiated by activation of various receptor tyrosine kinases. These proteins share a conserved, C-terminal cysteine-rich region, the SPR domain. This domain has been defined as a novel cytosol to membrane translocation domain. It has been found to be a PtdIns(4,5)P2-binding domain that targets the proteins to a cellular localization that maximizes their inhibitory potential. It also mediates homodimer formation of these proteins.