Phosphorylation src family kinases. Medical search. Frequent questions

Proto-oncogene tyrosine-protein kinase Fyn (p59-FYN, Slk, Syn, MGC45350, Gene ID 2534) is an enzyme that in humans is encoded by the FYN gene. (wikipedia.org)
Fyn is a member of the protein-tyrosine kinase oncogene family. (wikipedia.org)
The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the fyn-binding protein. (wikipedia.org)
Fyn is a tyrosine-specific phospho-transferase that is a member of the Src family of non-receptor tyrosine protein kinases. (wikipedia.org)
Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. (wikipedia.org)
note that PP2 also inhibits other tyrosine protein kinases such as Abl, PDGFR and c-Kit. (wikipedia.org)
Src and other Src family protein tyrosine kinases are proto-oncogenes that play key roles in regulating cell growth and differentiation. (rndsystems.com)
Protein Kinases Promising Targets for Anticancer Drug Researc. (intechopen.com)
Since oxidative stress activates protein kinase D1 (PKD1) in tumor cells, we investigated the effect of excitotoxicity on neuronal PKD1 activity. (nature.com)
Protein kinase D1 (PKD1), together with PKD2 and PKD3, constitute a family classified within the calcium/calmodulin-dependent protein kinase superfamily 7 . (nature.com)
Excitotoxic production of ROS elevates death-associated protein kinase (DAPK) activity, which provokes neuronal apoptosis in cerebral ischemia and seizure models 8 . (nature.com)
The ErbB inhibitor PD158780 and the mitogen-activated protein kinase kinase inhibitor U0126 also markedly inhibited NHK proliferation, migration, and amphiregulin production. (aspetjournals.org)
An in vitro immunocomplex kinase assay indicated that the rpS3 protein acts as a substrate for Lyn, which phosphorylates the Y167 residue of rpS3. (bmbreports.org)
L ike protein phosphorylation by kinases, protein ubiquitylation regulates many aspects of cell function and provides a wealth of drug target opportunities across many therapeutic areas including cancer, cardiovascular, metabolism, inflammation, neurodegeneration and infectious diseases. (ddw-online.com)
However, over the same period protein kinases have rapidly become one of the most significant classes of drug targets for the pharmaceutical industry, with the global market for kinase therapies being about US$15 billion per annum in 2010 and this value is predicted to double by 2020 (3). (ddw-online.com)
Research on protein kinases is now reported to account for approximately 30% of the drug discovery programmes in the pharmaceutical industry and more than 50% of cancer research and development (3). (ddw-online.com)
CD4 is noncovalently associated via the cytoplasmic domain with the protein-tyrosine kinase p56(lck), a member of the src protein-tyrosine kinase family. (mssm.edu)
Upon activation of protein kinase C by phorbol ester, CD4 is phosphorylated on cytoplasmic serine residues and internalized from the cell surface, and disruption of the CD4- p56(lck) complex occurs. (mssm.edu)
The exact relationship between these events is likely to be functionally significant, as cytoplasmic-domain serine phosphorylation and internalization have been shown to regulate the function of receptors that possess intrinsic protein-tyrosine kinase activity. (mssm.edu)
Following tyrosine phosphorylation by Src family kinases, PAG binds and thereby activates the protein tyrosine kinase Csk, the major negative regulator of the Src family kinases. (exbio.cz)
Signaling via the B-cell receptor in B cells or high affinity IgE receptor (FcepsilonRI) in mast cells leads to PAG increased tyrosine phosphorylation and Csk binding, while T cell receptor signaling causes PAG dephosphorylation, loss of Csk binding and increased activation of the protein tyrosine kinase Lck. (exbio.cz)
Vang T, Abrahamsen H, Myklebust S, Horejsi V, Tasken K: Combined spatial and enzymatic regulation of Csk by cAMP and protein kinase a inhibits T cell receptor signaling. (exbio.cz)
Here, we mechanically extended bacterially expressed Cas substrate domain protein (CasSD) in vitro and found a remarkable enhancement of phosphorylation by Src family kinases with no apparent change in kinase activity. (utmb.edu)
Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic development, cell proliferation, survival, differentiation, chemotaxis and migration. (scbdd.com)
Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the activation of protein kinase C. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to the activation of the AKT1 signaling pathway. (scbdd.com)
Stimulation of 3T3-L1 adipocytes with insulin significantly increased the tyrosine phosphorylation of caveolin and a 29-kD caveolin-associated protein in caveolin-enriched Triton-insoluble complexes. (rupress.org)
The insulin-dose responses for the tyrosine phosphorylation of caveolin and the 29-kD caveolin-associated protein paralleled those for the phosphorylation of the insulin receptor. (rupress.org)
The stimulation of caveolin tyrosine phosphorylation was specific for insulin and was not observed with PDGF or EGF, although PDGF stimulated the tyrosine phosphorylation of the 29-kD caveolin-associated protein. (rupress.org)
Increased tyrosine phosphorylation of caveolin, its associated 29-kD protein, and a 60-kD protein was observed in an in vitro kinase assay after incubation of the caveolin-enriched Triton-insoluble complexes with Mg-ATP, suggesting the presence of an intrinsic tyrosine kinase in these complexes. (rupress.org)
In addition, these complexes contain a 60-kD kinase detected in an in situ gel kinase assay and an approximately 60 kD protein that cross-reacts with an antibody against the Src-family kinase p59Fyn. (rupress.org)
This phosphorylation has previously been identified in cell lines via EGFR and Src signalling pathways, where it has been shown to alter the interaction between Ago2 and the miRNA maturation protein Dicer, but has never before been identified in neuronal signalling. (ukri.org)
Metformin increases AMP-activated protein kinase (AMPK) signaling, decreases mammalian target of rapamycin (mTOR) signaling, and decreases glucose production in fetal and juvenile hepatocytes. (bvsalud.org)
PP1 studies have proved its ability to potently inhibit Lck and Fyn (FynT), IL-2 gene activation in T lymphocytes, and anti-CD3-induced protein tyrosine phosphorylation. (cellgs.com)

The capacitation associated tyrosine phosphorylation is greatly reduced in the presence of Src specific inhibitors (SU6656 and SKI606) in vivo. (umass.edu)
As a means of control for the activity of Src inhibitors in our system, parallel experiments assaying the activity of PKA both in vivo and in vitro were realized. (umass.edu)
Surprisingly, Src inhibitors down regulates the phosphorylation of serine/threonine residues that correlate on earlier events in the capacitation, as assayed by western blot with PKA substrates antibody. (umass.edu)
However, in vitro kinase activity of PKA showed no effect of Src inhibitors in the phosphorylation of the PKA specific substrate, kemptide. (umass.edu)
and potent inhibition of NHK proliferation and migration by two Src family kinase inhibitors PP1 and PD173952. (aspetjournals.org)
Moreover, the effect of Src family kinase inhibitors on EGF-stimulated ERK phosphorylation was transient, prompting a search for other targets of Src family kinase action. (aspetjournals.org)
Furthermore, by adding various kinase inhibitors, we confirmed that the phosphorylation status of rpS3 was regulated by both Lyn and doxorubicin, and the phosphorylation of rpS3 by Lyn increased drug resistance in cells by upregulating p-glycoprotein translation. (bmbreports.org)

We have found that the inactive conformations of the Tec kinase Itk and Src preferentially bind ADP over ATP, stabilising both proteins. (rcsb.org)
In this work we used a combination of two dimensional gel electrophoresis and mass spectrometry to identify proteins that undergo tyrosine phosphorylation during capacitation. (umass.edu)
Some of the identified proteins are the mouse orthologues of human sperm proteins known to undergo tyrosine phosphorylation. (umass.edu)
In addition to previously described proteins, we identified two testis-specific aldolases as substrates for tyrosine phosphorylation. (umass.edu)
Because of the importance of glycolysis for sperm function, we hypothesize that tyrosine phosphorylation of these proteins can play a role in the regulation of glycolysis during capacitation. (umass.edu)
We demonstrate, by confocal microscopy, that stimulation of Caco-2 cells with ATP results in the translocation of active MAPKs to the nucleous where they induce the expression of c-Fos and Jun family proteins, the phosphorylation of ATF-1, ATF-2 and JunD transcription factors and stimulate Caco-2 cell proliferation. (conicet.gov.ar)
All NSP proteins contain an NH 2 -terminal SH2 (Src homology domain 2) domain, a central proline/serine-rich domain, and a COOH-terminal domain with modest homology to Ras subfamily GDP-exchange factors (GEFs). (molvis.org)
Podosomes are structurally divided into a core, which mainly contains proteins involved in actin polymerization (such as WASP, the Arp2/3 complex and cortactin ), and a surrounding ring populated by integrin receptors and adhesion proteins (for example, paxillin and focal adhesion kinase (FAK/Pyk2) ) [15] . (cellmigration.org)
Demographic and that this particular family of angiogenic clinical data were collected during routine proteins plays an important role in placental obstetric visits. (who.int)

This family also includes Abl, Src, focal adhesion kinase and Janus kinase. (wikipedia.org)

The GDNF family ligands (GFLs) function through a glycosyl-phosphatidylinositol-(GPI) anchored coreceptor, GDNF family receptor alpha (GFRα), and rearranged during transfection (RET), a well-known receptor tyrosine kinase involved in kidney development, spermatogonial stem cell maintenance, and the development and maintenance of the sympathetic, parasympathetic, and enteric nervous systems [ 1 , 2 ]. (medsci.org)

and liver fibrosis resolved on treatment with the Src kinase inhibitor dasatinib. (nature.com)
Two patients with truncating mutations had liver fibrosis that in one patient resolved on treatment with the Src kinase inhibitor dasatinib. (nature.com)
The epidermal growth factor receptor (EGFR) specific inhibitor AG1478 decreased ERK1/2, JNK1/2 and p38 MAPK phosphorylation by ATP, suggesting that EGFR transactivation is important for ATP-mediated stimulation of MAPKs in this intestinal cell line. (conicet.gov.ar)
Moreover, a comparison of the apo- and inhibitor-bound Lyp structures reveals that the Lyp-specific region S 35 TKYKADK 42 , which harbors a PKC phosphorylation site, could adopt either a loop or helical conformation. (elsevierpure.com)
PP1 is a selective and potent Src-family tyrosine kinase inhibitor. (cellgs.com)

c-Src (cellular Src), encoded by Src gene, is a non-receptor tyrosine kinase first isolated as the normal cellular homolog to the potent avian sarcoma viral transforming oncogene v-Src [ 4 ]. (intechopen.com)
It has been suggested that the non receptor tyrosine kinase Src family is involved in the capacitation associated phosphorylation cascade. (umass.edu)
Initial observation that COX2 forms adduct with non-receptor tyrosine kinase FYN, prompted us to study FYN-mediated post-translational regulation of COX2. (oncotarget.com)

Together, these observations demonstrate that one or more Src family kinases act upstream as well as downstream of ErbB1 to promote amphiregulin-dependent autocrine stimulation of NHKs and suggest that autocrine NHK proliferation is more dependent upon ERK activation than upon Tyr 845 phosphorylation. (aspetjournals.org)
Thus, we propose that Cas acts as a primary force sensor, transducing force into mechanical extension and thereby priming phosphorylation and activation of downstream signaling. (utmb.edu)
Thus, the insulin-dependent tyrosine phosphorylation of caveolin represents a novel, insulin-specific signal transduction pathway that may involve activation of a tyrosine kinase downstream of the insulin receptor. (rupress.org)
Research indicates that PP1 effectively blocks LPA and EGF-enhanced tyrosine phosphorylation, MAPK activation downstream of EGFR, Rsk-1 (p90RSK) activation by H 2 O 2 , Kit and Bcr-Abl tyrosine kinases, and degrades RETMEN2A and RETMEN2B oncoproteins via proteosomal targeting. (cellgs.com)

We provide evidence that the status of Ser-35 phosphorylation may dictate the conformational state of the insert region and thus Lyp substrate recognition. (elsevierpure.com)

c-Src tyrosine kinase plays an important role in signal transduction pathways, where its activity is regulated by phosphorylation of the two tyrosine residues. (intechopen.com)
Looking upstream the kinase cascade, the identity of the kinase (s) that brings about the phosphorylation of the tyrosine residues remains to be elucidated. (umass.edu)

In addition, western blot analysis revealed that ATP-induced phosphorylation of MAPKs in Caco-2 cells was dependent on calcium influx and intracellular calcium release, Src-family tyrosine kinases, and partially dependent on the cAMP/PKA and PKC pathways. (conicet.gov.ar)
Lyn, a tyrosine kinase that is activated by double-stranded DNA-damaging agents, is involved in various signaling pathways, such as proliferation, apoptosis, and DNA repair. (bmbreports.org)
Activated tyrosine kinases generate a second wave of messengers by activating serine/threonine kinases or phosphatases pathways. (medscape.com)
Three major pathways have been identified: the inositol phospholipid hydrolysis pathway, the phosphatidyl inositol-3-kinase pathway, and the Ras pathway. (medscape.com)

Furthermore, disruption of the CD4-p56(lck) complex appears to depend on the integrity of the cytoplasmic-domain serine at position 408, probably due to a requirement for phosphorylation. (mssm.edu)

PP1 inhibits anti-CD3-induced T cell tyrosine phosphorylation, TcR-induced T cell proliferation, and IL-2 gene induction. (cellgs.com)

Using this, we showed that the tyrosine kinase ZAP-70, which is critical for T cell signaling, discriminates substrates through an electrostatic selection mechanism encoded within its catalytic domain (Shah et al. (escholarship.org)
Using this approach, we find a difference in the electrostatic recognition of substrates between the closely related Src-family kinases Lck and c-Src. (escholarship.org)

the second activates Bruton tyrosine kinase and Syk. (medscape.com)

Fyn is a 59-kDa member of the Src family of kinases typically associated with T-cell and neuronal signaling in development and normal cell physiology. (wikipedia.org)
Here, we show that the non-receptor Src family tyrosine kinases, SRC64B and SRC42A, are involved in WNT5-mediated signaling through Derailed in the Drosophila embryonic central nervous system. (biologists.com)
The mammalian orthologs of Derailed and SRC64B also form complexes, suggesting that Src roles in RYK signaling are conserved. (biologists.com)
Although several lines of evidence also suggest important interactions of ErbB and Src family kinase signaling in normal epithelial cells, little is known about the mechanism of this interaction. (aspetjournals.org)
We demonstrate that Ser-35 phosphorylation impairs Lyp's ability to inactivate the Src family kinases and down-regulate T cell receptor signaling. (elsevierpure.com)

Phosphorylation at Y419 of human Src up-regulates kinase activity, while phosphorylation at Y530 inactivates Src. (rndsystems.com)

P rotein kinases, on the other hand, have become one of the most important classes of drug targets for the pharmaceutical industry over the last decade, following on from the exploitation of kinase-focused libraries for at least the last two decades. (ddw-online.com)
Target-focused compound libraries have been a key enabling component of the tool kit opening up kinase drug discovery, consisting of collections of compounds designed to interact with a family of related kinase targets (4). (ddw-online.com)

Phosphorylation of the AChR β subunit is correlated with increased rapsyn/AChR binding, suggesting that the effect of βY390 phosphorylation on clustering is mediated by rapsyn. (jneurosci.org)
Together, these findings suggest that agrin-induced phosphorylation of the β subunit motif increases the stoichiometry of rapsyn binding to the AChR, thereby helping to stably cluster the receptor and anchor it at high density in the postsynaptic membrane. (jneurosci.org)
Indeed, we have shown previously that mutation of a tyrosine phosphorylation site in the long cytoplasmic loop of the β subunit impairs agrin-induced cytoskeletal anchoring and aggregation of mutant AChR in muscle cells ( Borges and Ferns, 2001 ). (jneurosci.org)

Fyn is functionally distinct from its family members in that it interacts with FAK and paxillin (PXN) in the regulation of cell morphology and motility. (wikipedia.org)

Oxidative stress is an important activator of PKD1 in cellular models, but its capacity to activate this kinase in vivo is largely unknown. (nature.com)

Our results showed that ATP induces the phosphorylation of MAPKs in a time and dose-dependent manner, peaking at 5 min at 10 M ATP. (conicet.gov.ar)

Members of the RYK/Derailed family have recently been shown to regulate axon guidance in both Drosophila and mammals by acting as Wnt receptors. (biologists.com)
Immunoglobulin-like transcripts are a family of inhibitory and stimulatory cell surface immune receptors. (rupress.org)

2016). Here, we expand this high-throughput platform to analyze the intrinsic specificity of any tyrosine kinase domain against thousands of peptides derived from human tyrosine phosphorylation sites. (escholarship.org)

Cell growth, global phosphotyrosine elevation, and c-Met phosphorylation through Src family kinases in colorectal cancer cells. (cellosaurus.org)

Using an antibody that recognized extended CasSD in vitro, we observed Cas extension in intact cells in the peripheral regions of spreading cells, where higher traction forces are expected and where phosphorylated Cas was detected, suggesting that the in vitro extension and phosphorylation of CasSD are relevant to physiological force transduction. (utmb.edu)

Moreover, MAPKs participate in the induction and phosphorylation of the dual phosphatase MKP-1, which is known to inactivate ERK, JNK and p38 MAPK by dephosphorylating two critical sites in the activation loop. (conicet.gov.ar)

We characterize the role of increased Lyn kinase activity in neutrophils, endothelial cells and lesional liver biopsies and utilized an iPSC-derived endothelial cell platform for disease modeling of neutrophilic vasculitis and to screen and evaluate drug efficacy. (nature.com)
Vascular endothelial growth factor A (VEGFA) and inflammatory cytokines both induce adherens junction disassembly by Src family kinase-mediated phosphorylation of Vascular endothelial (VE)-cadherin. (icgeb.org)

The sequence contains a conserved tyrosine (Y390) whose phosphorylation is induced by agrin and whose mutation abolished clustering of β loop chimeras and their ability to inhibit agrin-induced clustering of the endogenous AChR. (jneurosci.org)
We report that FYN phosphorylates human COX2 on Tyr 446, and while corresponding phospho-mimetic COX2 mutation promotes COX2 activity, the phosphorylation blocking mutation prevents FYN-mediated increase in COX2 activity. (oncotarget.com)

The BTK gene is present on Xq21.3-q22, and its defect results in deficiency of Bruton tyrosine kinase. (medscape.com)

Basal levels of p130Cas phosphorylation were higher in AND-34 +/+ than in AND-34 −/− lens epithelium. (molvis.org)
Previously, we showed that tyrosine phosphorylation of p130Cas (Cas) in a cytoskeletal complex is involved in force-dependent activation of the small GTPase Rap1. (utmb.edu)

Fyn is a member of the Src-family of kinases (SFK), the first proto-oncogene to be identified. (wikipedia.org)

Die Rolle von Src-Kinasen wurde durch pharmakologische Inhibition analysiert. (uni-wuerzburg.de)
Außerdem konnte demonstriert werden, dass die Inhibition von Src-Kinasen den Anstieg der Endothelpermeabilität signifikant reduziert. (uni-wuerzburg.de)

While Akt Ser 473 phosphorylation was readily detectable in AND-34 +/+ lens epithelial cells, it was markedly reduced in the AND-34 −/− lens epithelium. (molvis.org)

c-Src tyrosine kinase consists of the N-terminal unique region, the Src homology 3 (SH3), SH2, linker, kinase domain, and the regulatory C-terminal tail. (intechopen.com)

Phosphorylation of Syk Activation Loop Tyrosines Is Essential for Syk Function. (crossref.org)
Following B-cell receptor activation, 2 waves of tyrosine kinase phosphorylation occur. (medscape.com)
Next-generation sequencing identified two de novo truncating variants in the Src-family tyrosine kinase, LYN , p.Y508*, p.Q507* and a de novo missense variant, p.Y508F, that result in constitutive activation of Lyn kinase. (nature.com)
Allosteric activation of both Itk and Src depends critically on the disruption of a conserved hydrophobic stack that accompanies regulatory domain displacement. (rcsb.org)
In summary, we propose a universal mechanism for the activation and autoinhibition of the Src and Tec kinases. (rcsb.org)
8000 Bahía Blanca, Argentina In the present work, we examined the role of ATP in the activation of the MAP kinases (MAPKs) ERK1/2, JNK1/2 and p38 and their involvement in the modulation of transcription factors and proliferation of human colon cancer Caco-2 cells. (conicet.gov.ar)
Phosphorylation of SHC1, or of the C-terminus of PTPN11, creates a binding site for GRB2, resulting in the activation of HRAS, RAF1 and down-stream MAP kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. (scbdd.com)
Promotes phosphorylation and activation of SRC family kinases. (scbdd.com)

Here, we define a phosphorylation-dependent binding site on the receptor that mediates agrin-induced clustering. (jneurosci.org)

The Tec kinases, closely related to Src family kinases, are essential for lymphocyte function in the adaptive immune system. (rcsb.org)

Promotes phosphorylation of PDCD6IP/ALIX and STAM. (scbdd.com)

Src family activity is regulated by tyrosine phosphorylation at two sites with opposing effects. (rndsystems.com)
Little is known about how the kinase activity-deficient RYKs transduce Wnt signals. (biologists.com)
Derailed and SRC64B form a complex, which contains catalytically active SRC64B, the formation or stability of which requires SRC64B kinase activity. (biologists.com)

Using these, models, we have studied the role of VE-cadherin phosphorylation and adherens junction disintegration in a number of diseases including cancer, retinopathy and myocardial infarction. (icgeb.org)

We demonstrate that Itk adopts the same conformation as Src and that the autoinhibited conformation of Src is independent of its C-terminal tail. (rcsb.org)

Glial cell line-derived neurotrophic factor family receptor alpha (GFRα) members have been widely connected to the mechanisms contributing to cell growth, differentiation, cell migration and tissue maturation. (medsci.org)
The glial cell line-derived neurotrophic factors (GDNFs), a family of neurotrophic factors, were initially thought to be able to regulate the growth, survival, and differentiation of neural-derived cell types. (medsci.org)

Our findings reveal a critical role for Lyn kinase in modulating inflammatory signals, regulating microvascular permeability and neutrophil recruitment, and in promoting hepatic fibrosis. (nature.com)

Tyrosine (Tyr) 845 of ErbB1 is phosphorylated by Src and has been implicated in control of malignant behavior. (aspetjournals.org)

Herein, we demonstrated that rpS3 and Lyn interact with each other, and the phosphorylation of rpS3 by Lyn, causing ribosome heterogeneity, upregulates the translation of p-glycoprotein, which is a gene product of multidrug resistance gene 1. (bmbreports.org)

It encodes a membrane-associated tyrosine kinase that has been implicated in the control of cell growth. (wikipedia.org)
Li Q, Cao Z, Zhao S. The Emerging Portrait of Glial Cell Line-derived Neurotrophic Factor Family Receptor Alpha (GFRα) in Cancers. (medsci.org)

c-Src potentiates proliferation, survival, and invasiveness in response to epidermal growth factor (EGF) in human mammary carcinoma cells. (aspetjournals.org)

Anatomy25

Organisms10

Diseases1

Chemicals and Drugs156

Analytical, Diagnostic and Therapeutic Techniques and Equipment14

Phenomena and Processes46

Technology, Industry, Agriculture1

Information Science3

Protein33

Inhibitors7

Proteins9

Focal adhesi1

Phosphatidylinositol1

Inhibitor5

Receptor tyrosi3

Downstream4

Substrate1

Tyrosine residues2

Pathways4

Serine1

Inhibits1

Substrates2

Activates1

Signaling5

Regulates1

Targets2

Subunit3

Regulation1

Vivo1

Induces1

Receptors2

Intrinsic1

Phosphotyrosine1

Antibody1

MAPK1

Endothelial2

Mutation2

Bruton1

P130Cas2

Oncogene1

Inhibition2

Epithelial cells1

Homology1

Activation8

Mediates1

Closely related1

Promotes1

Activity3

Adherens1

Demonstrate1

Differentiation2

Inflammatory1

Malignant1

Gene1

Cell2

Epidermal1