InhibitorReceptor tyrosiInhibitorsEncodesAnaplastic LymphoResiduesTransmembraneEGFRPathwayCAMP-dependReduced tyrosine phosphorylationGeneRegulate tyrosineSignal transductionPathwaysInhibitionUniProtReceptorsPhosphataseSubstratesOncogenePhosphorylatesInhibitsMalignantActivationEnzymeEpidermal growth fCatalyticCellularMass spectrometryPlasma membraneConstitutiveUbiquitin proteinNegativelyEpithelialPTKsAssayRecombinantCytoplasmicSubunitHomologyNegative regulatorsOncogenicAmino acidsPhosphatidylinositolTumor suppressorTissuesApoptosisRegulationDifferentiationLocusPhosphoinositideHumanStimulationCellFamilyInteractions
Inhibitor7
- Chloroquine inhibited the membrane bound PTK activity in a dose dependent manner (IC 50 = 45 μ M ). Kinetic studies show that chloroquine is a competitive inhibitor of PTK with respect to peptide substrate and noncompetitive with respect to ATP indicating that chloroquine inhibits PTK activity by binding with protein substrate binding site. (niscair.res.in)
- Is classified as a tyrosine kinase inhibitor. (pharmacology2000.com)
- A physiological mathematical model of chronic myeloid leukemia, validated by experiments in transgenic mice and clinical data, identifies mechanisms underlying the response to tyrosine kinase inhibitor therapy, predicts biomarkers of primary resistance, and suggests new strategies to improve treatment outcomes. (elifesciences.org)
- The introduction of imatinib, a selective inhibitor of the ABL tyrosine kinase, has revolutionized the treatment and the outcome of this subset of patients [ 1 ]. (hindawi.com)
- Like sorafenib, lapatinib is a protein kinase inhibitor shown to decrease tumor-causing breast cancer stem cells. (hmdb.ca)
- Imatinib mesylate (IM), a potent inhibitor of the BCR/ABL tyrosine kinase, has become standard first-line therapy for patients with chronic myeloid leukemia (CML), but the frequency of resistance increases in advancing stages of disease. (lu.se)
- Critically, the combination of a tyrosine kinase inhibitor (TKI), i.e. (lu.se)
Receptor tyrosi3
- Orthologous to human ABL2 (ABL proto-oncogene 2, non-receptor tyrosine kinase). (nih.gov)
- A Role for the Non-Receptor Tyrosine Kinase Abl2/Arg in Experimental Neuroinflammation. (nih.gov)
- FLT3 (FMS-related tyrosine kinase 3) located on chromosome 13q12.2 encodes a receptor tyrosine kinase (RTK) that activates the Ras and PI3 kinase pathway leading to the increased proliferation and inhibition of apoptosis in hemopoietic progenitor cells [ 7 ]. (hindawi.com)
Inhibitors3
- Treatments with pertussis-toxin, inhibition of phospholipase C and protein kinase C inhibitors and chelation of free cytosolic calcium did not change the bradykinin-induced inhibition of phosphotyrosine kinase. (nih.gov)
- A series of pyrazolylpyrimidine scaffold based Syk inhibitors were synthesized and evaluated for their biological activities and selectivity. (rcsb.org)
- Before the advent of tyrosine kinase inhibitors (TKIs), the outcome of Ph+ ALL patients not eligible for allogeneic stem cell transplant (allo-SCT) was characterized by an extremely poor prognosis, a weak response to most chemotherapy combinations, short remission durations, and poor survival rates. (hindawi.com)
Encodes5
- q11) resulting in a chimeric bcr-abl (e1a2 breakpoint) fusion gene that encodes a 190 KD protein (p190) with constitutively active tyrosine kinase activity that can alter multiple signaling pathways, contributing to tumor growth and proliferation. (hindawi.com)
- This gene encodes a protein containing a C3HC4-type RING finger domain, which is a specialized type of Zn-finger that binds two atoms of zinc and is thought to be involved in mediating protein-protein interactions. (cancerindex.org)
- From NCBI Gene: The proto-oncogene MET product is the hepatocyte growth factor receptor and encodes tyrosine-kinase activity. (nih.gov)
- This gene encodes one of the three members of the human AKT serine-threonine protein kinase family which are often referred to as protein kinase B alpha, beta, and gamma. (senescence.info)
- PAG3 encodes a multidomain protein containing an N-terminal alpha-helical region with a coiled-coil motif, followed by a pleckstrin homology (PH) domain, an Arf-GAP domain, an ankyrin homology region, a proline-rich region, and a C-terminal Src homology 3 (SH3) domain. (novusbio.com)
Anaplastic Lympho2
- This gene is also a translocation partner in anaplastic large cell lymphoma and inflammatory myofibroblastic tumor cases, where a t(2;17)(p23;q25) translocation has been identified with the anaplastic lymphoma kinase (ALK) gene on chromosome 2, and a t(8;17)(q24;q25) translocation has been identified with the MYC gene on chromosome 8. (cancerindex.org)
- Anaplastic lymphoma kinase (ALK) protein may be detected in most cases (60-70%) of systemic ALCL by immunohistochemistry. (medscape.com)
Residues6
- This enzyme phosphorylates tyrosine residues located in the C-terminal end of Src-family kinases (SFKs) including SRC, HCK, FYN, LCK, LYN and YES1. (wikipedia.org)
- Ectopic up-regulation of PTPRD in neuroblastoma dephosphorylates tyrosine residues in AURKA resulting in a destabilization of this protein culminating in interfering with one of AURKA's primary functions in neuroblastoma, the stabilization of MYCN protein, the gene of which is amplified in approximately 25 to 30% of high risk neuroblastoma. (biomedcentral.com)
- Three sequential phosphorylation events on specific residues of p27, regulate the activity of these complexes and ultimately control cell cycle proliferation or arrest. (lu.se)
- Notably, the first two post-translational modifications, which are required for the initial activation of these complexes, occur on solvent inaccessible (i.e., buried) tyrosine residues. (lu.se)
- If these residues are inaccessible to kinases, how do they get phosphorylated then? (lu.se)
- More generally, bioinformatics analyses have shown that ~15% of all phosphorylated residues are buried in the non-phosphorylated state, suggesting that transient exposure might be a general mechanism involved in protein regulation. (lu.se)
Transmembrane3
- To inhibit SFKs, CSK is then recruited to the plasma membrane via binding to transmembrane proteins or adapter proteins located near the plasma membrane and ultimately suppresses signaling through various surface receptors, including T-cell receptor (TCR) and B-cell receptor (BCR) by phosphorylating and maintaining inactive several effector molecules. (wikipedia.org)
- and transmembrane receptor protein tyrosine kinase signaling pathway. (nih.gov)
- Protein tyrosine phosphatase receptor delta ( PTPRD ) is an important regulator of axon growth and guidance and is highly expressed in the central nervous system where it functions as a transmembrane homophilic neuronal cell adhesion molecule [ 1 ]. (biomedcentral.com)
EGFR5
- This peptide is a potential substrate for EGFR protein tyrosine kinases. (anaspec.com)
- Gefitinib administration prevents tyrosine residue of autophosphorylation of the EGFR receptor. (pharmacology2000.com)
- We have shown that all mammalian Cbl proteins mediate ubiquitination and degradation of the activated EGFR as well as other components of the signaling complex. (cancer.gov)
- It is a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. (antibodyguide.com)
- It inhibits both ERBB2 and EGFR activity. (antibodyguide.com)
Pathway3
- Taken together, these data suggest for the first time that, in proliferating rat mesangial cells, B2 receptor stimulation is able to induce, via a pertussis insensitive pathway, the inhibition of tyrosine kinase activity and mesangial cell proliferation. (nih.gov)
- We have recently shown that this same pathway modulates the content of integral membrane proteins and, in collaborative studies, that it is also involved in maintenance of the sterol composition of the plasma membrane. (berkeley.edu)
- AKT proteins also participate in the mammalian target of rapamycin (mTOR) signalling pathway which controls the assembly of the eukaryotic translation initiation factor 4F (eIF4E) complex and this pathway, in addition to responding to extracellular signals from growth factors and cytokines, is disregulated in many cancers. (senescence.info)
CAMP-depend1
- Role of hormone-sensitive low Km cAMP phosphodiesterase in regulation of cAMP-dependent protein kinase and lipolysis in rat adipocytes. (aspetjournals.org)
Reduced tyrosine phosphorylation1
- Western blot analysis of phosphotyrosinated proteins demonstrated that BK reduced tyrosine phosphorylation of several proteins among which we identified the 125-focal adhesion kinase. (nih.gov)
Gene12
- Tyrosine-protein kinase CSK also known as C-terminal Src kinase is an enzyme that, in humans, is encoded by the CSK gene. (wikipedia.org)
- S364A - Strong decrease of phosphorylation by PRKACA (the catalytic subunit of protein kinase A). Csk's interaction with a phosphatase ("Lyp", gene product of PTPN22) is possibly associated with the increased autoimmune diseases associated with PTPN22 mutations. (wikipedia.org)
- The Abl-related gene (Arg) requires its F-actin-microtubule cross-linking activity to regulate lamellipodial dynamics during fibroblast adhesion. (nih.gov)
- Note that by convention gene names are italicized and the proteins they make are not. (cancerquest.org)
- As an example TP 53 refers to the gene and p53 refers to the protein. (cancerquest.org)
- What does this gene/protein do? (cancerindex.org)
- Subsequent phosphorylation of both threonine residue 308 and serine residue 473 is required for full activation of the AKT1 protein encoded by this gene. (senescence.info)
- Brain and muscle Arnt-like protein-1 ( BMAL1 ) knockout mice exhibit accelerated aging, abnormal glucose metabolism, and impaired adipocyte differentiation, among other phenotypes, which are effects associated with the BMAL1 gene. (go.jp)
- As opposed to other styles of muscles dystrophy, where mutations take place in genes encoding structural protein, calpainopathy was the initial reported kind of dystrophy predetermined by mutations within a gene encoding a proteolytic enzyme. (exposed-skin-care.net)
- You can find over 440 noted mutations within the calpain 3 gene up to now, included in this 212 (50%) are missense mutations, a lot of which alter its catalytic activity (22). (exposed-skin-care.net)
- The ROR2 gene provides instructions for making a protein whose function is not well understood. (medlineplus.gov)
- Unlike the mutations that cause Robinow syndrome (described above), the ROR2 gene mutations that cause brachydactyly type B1 are described as "gain-of-function" because they appear to cause the ROR2 protein to be continuously active. (medlineplus.gov)
Regulate tyrosine2
- We are investigating the function of Cbl proteins, a family of proteins that regulate tyrosine kinase activity. (cancer.gov)
- Protein tyrosine phosphatase receptor delta (PTPRD) is a member of a large family of protein tyrosine phosphatases which negatively regulate tyrosine phosphorylation. (biomedcentral.com)
Signal transduction1
- FLT3 ( FMS -related tyrosine kinase 3) acts as an oncogene in myeloid neoplasms which is associated with several signal transduction pathways. (hindawi.com)
Pathways3
- AKT/PI3K forms a key component of many signalling pathways that involve the binding of membrane-bound ligands such as receptor tyrosine kinases, G-protein coupled receptors, and integrin-linked kinase. (senescence.info)
- These pathways control the activity of genes needed at specific times, and they regulate the interactions between cells as organs and tissues are forming. (medlineplus.gov)
- Loss of ROR2 protein function impairs chemical signaling pathways that are important for normal development, particularly the formation of bones in the face, spine, and limbs. (medlineplus.gov)
Inhibition5
- The results suggest that maturation of malaria parasite is related to PTK and inhibition of this activity by chloroquine could provide a hypothesis to explain the mechanism of action of chloroquine. (niscair.res.in)
- We next found that BK induced a dose-dependent inhibition of phospho-tyrosine kinase activity. (nih.gov)
- Transcriptional activation of the orphan nuclear receptor Nurr1 by ligands targeting its heterodimer partner retinoid X receptor alpha (RXRα) occurs through a nonclassical pharmacological mechanism involving ligand-binding domain protein-protein interaction inhibition. (elifesciences.org)
- We find that noncatalytic inhibition follows the same activity dependence pattern as catalytic modulation (phosphorylation): the efficacy and apparent affinity of genistein inhibition are much higher for closed than for fully activated channels. (silverchair.com)
- as a cell surface-associated protein, it is easily accessible to drugs and as a kinase it is amenable to targeted inhibition by small molecules. (antibodyguide.com)
UniProt1
- Universal protein resource accession number P41240 for "Tyrosine-protein kinase CSK" at UniProt. (wikipedia.org)
Receptors4
- The pheromone receptors have seven hydrophobic segments and are coupled to a heterotrimeric G protein. (berkeley.edu)
- Molecular targets acted on by products in development for blood pressure disorders include angiotensin receptors, tyrosine protein kinases and phosphodiesterases. (openpr.com)
- Cerebral muscarinic acetylcholine receptors interact with three kinds of GTP-binding proteins in a reconstitution system of purified components. (aspetjournals.org)
- Activation of the protein-tyrosine kinase activity of the receptors occurs by ligand-induced dimerization or heterodimerization of PDGF receptor types. (bvsalud.org)
Phosphatase1
- PTP, protein tyrosine phosphatase. (silverchair.com)
Substrates1
- Detection of nerve growth factor and epidermal growth factor-regulated protein kinases in PC12 cells with synthetic peptide substrates. (aspetjournals.org)
Oncogene1
- A key feature of oncogene activity is that a single altered copy leads to unregulated growth. (cancerquest.org)
Phosphorylates1
- The protein tyrosine kinase (PTK) Lck phosphorylates the ζ-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. (harvard.edu)
Inhibits2
- Irreversibly inhibits kinase activity. (pharmacology2000.com)
- It binds to the extracellular domain of ERBB2 and inhibits its activity. (antibodyguide.com)
Malignant1
- These AKT proteins therefore regulate a wide variety of cellular functions including cell proliferation, survival, metabolism, and angiogenesis in both normal and malignant cells. (senescence.info)
Activation7
- Phosphorylation of Syk Activation Loop Tyrosines Is Essential for Syk Function. (crossref.org)
- The relationship between cell proliferation, protein tyrosine phosphorylation, phosphotyrosine kinase activity and bradykinin receptor activation in rat mesangial cells was investigated. (nih.gov)
- Activation of the pheromone receptor-coupled G protein initiates a four-tiered cascade of protein kinases, ultimately resulting in stimulation of a messenger-activated protein kinase or MAPK (Fus3) that translocates into the nucleus. (berkeley.edu)
- These studies suggest that PTKs affects RETα channels in two ways: (1) by catalyzing phosphorylation of the channel protein, and (2) by allosterically regulating channel activation. (silverchair.com)
- Calpain 3 provides 54 and 51% series homology towards the 80 kDa subunits of - and m-calpains, respectively, and stocks similar properties with one of these ubiquitously portrayed calpains such as for example Ca2+- reliant activation and maximal activity at natural pH (1). (exposed-skin-care.net)
- Wnt-5a signalling is thus involved in the activation of DDR1 as well as in hampering NFAT activity, both of which affect the migratory capacity of tumour cells. (lu.se)
- p27 is a protein that binds to and prevents the activation of different G1 and S phase cyclin-CDK complexes. (lu.se)
Enzyme1
- Protein tyrosine kinase (PTK) is an enzyme which mediates cell function, growth, metabolism and apoptosis. (journalcra.com)
Epidermal growth f1
- ERBB2 is a protein that is also known as HER2 (human epidermal growth factor receptor 2). (antibodyguide.com)
Catalytic1
- It has catalytic activity for class I and II ArfGAPs in vitro, and can bind the class III Arf ARF6 without immediate GAP activity. (novusbio.com)
Cellular1
- NLRP3/cryopyrin is a member of the NOD-like receptor (NLR) protein family that plays a pivotal role in the inflammatory response against pathogens and cellular damage. (nature.com)
Mass spectrometry1
- No mass spectrometry results found for this protein. (yeastrc.org)
Plasma membrane2
- We have shown that Ypk1, a member of the AGC class of protein kinases conserved from yeast to humans, is the essential target of and activated via phosphorylation by the plasma membrane-associated TORC2 complex. (berkeley.edu)
- The protein localizes in the Golgi apparatus and at the plasma membrane, where it colocalizes with protein tyrosine kinase 2-beta (PYK2). (novusbio.com)
Constitutive1
- Ph+ acute lymphoblastic leukemia (Ph+ ALL) is a high-risk acute leukemia with poor prognosis, in which the specific t(9;22)(q34;q11) translocation results in a chimeric bcr-abl (e1a2 breakpoint) and in a 190 KD protein (p190) with constitutive tyrosine kinase activity. (hindawi.com)
Ubiquitin protein1
- Cbl proteins belong to the RING finger class of ubiquitin protein ligases (E3s) and function as E3s for activated tyrosine kinases. (cancer.gov)
Negatively1
- 1) We study Cbl proteins, a family of ubiquitin ligases that negatively regulate signaling by receptor tyrosine kinases. (cancer.gov)
Epithelial2
- Human epithelial malignancies frequently display deregulated tyrosine kinase activity. (cancer.gov)
- Ongoing work is focused on understanding the biochemical and physiologic functions of the three mammalian Cbl proteins in epithelial cells and elucidating the differences in their specificity and/or function. (cancer.gov)
PTKs2
- Protein tyrosine kinases (PTKs) are believed to be implicated in the parasite growth, maturation and differentiation functions. (niscair.res.in)
- Rod cyclic nucleotide-gated (CNG) channels are modulated by changes in tyrosine phosphorylation catalyzed by protein tyrosine kinases (PTKs) and phosphatases (PTPs). (silverchair.com)
Assay1
- To determine the PTK activity in normal and leukemic animal universal tyrosine kinase assay kit were used. (journalcra.com)
Recombinant1
- The recombinant protein does not dimerize by itself in solution. (harvard.edu)
Cytoplasmic1
- The adaptor protein Grb2 is able to enhance the activity of the cytoplasmic tyrosine kinase Btk through a novel mechanism, revealing a new role for Grb2 in B-cell signaling. (elifesciences.org)
Subunit2
- Previously, we found that in addition to inhibiting tyrosine phosphorylation of the rod CNG channel α-subunit (RETα), genistein triggers a noncatalytic inhibitory interaction between the PTK and the channel. (silverchair.com)
- Interleukin 35 (IL35) may presumably signal via a complex that includes Tyrosine protein kinase JAK1 (JAK1) and JAK2 associated with Interleukin 6 receptor beta subunit (IL6ST) and Interleukin 12 receptor beta 2 subunit (IL12RB2) (Collison et al. (reactome.org)
Homology1
- These highly similar AKT proteins all have an N-terminal pleckstrin homology domain, a serine/threonine-specific kinase domain and a C-terminal regulatory domain. (senescence.info)
Negative regulators1
- Protein phosphatases act as negative regulators of AKT proteins by dephosphorylating AKT or PIP3. (senescence.info)
Oncogenic2
- As a molecular mechanism, we demonstrate that PTPRD interacts with aurora kinase A (AURKA), an oncogenic protein that is over-expressed in multiple forms of cancer, including neuroblastoma. (biomedcentral.com)
- Whereas the oncogenic Wnt-1 is the main Wnt protein investigated in breast cancer, very little work has been focused on Wnt-5a, a protein supposedly antagonizing the oncogenic effects of Wnt-1. (lu.se)
Amino acids1
- Some of these mutations change single protein building blocks (amino acids) in the ROR2 protein, while others lead to the production of an abnormally short, nonfunctional version of the protein. (medlineplus.gov)
Phosphatidylinositol1
- AKT proteins are recruited to the cell membrane by phosphatidylinositol 3,4,5-trisphosphate (PIP3) after phosphorylation of phosphatidylinositol 4,5-bisphosphate (PIP2) by PI3K. (senescence.info)
Tumor suppressor2
- PTPRD has a tumor suppressor function in neuroblastoma through AURKA dephosphorylation and destabilization and a downstream destabilization of MYCN protein, representing a novel mechanism for the function of PTPRD in neuroblastoma. (biomedcentral.com)
- We further demonstrate that PTPRD has a tumor suppressor function in neuroblastoma through dephosphorylating and destabilizing AURKA, leading to a downstream decrease of MYCN protein. (biomedcentral.com)
Tissues1
- Acute radiation syndromes can be caused by a sufficient dose of some internally deposited radionuclides that are widely distributed in tissues and organs and have a high specific activity. (msdmanuals.com)
Apoptosis2
- It does so by forming a multiprotein signaling complex, the NLRP3 inflammasome, with apoptosis-associated speck-like protein containing CARD (ASC) and caspase-1 1 . (nature.com)
- IM-induced autophagy did not involve c-Abl or Bcl-2 activity but was associated with ER stress and was suppressed by depletion of intracellular Ca2+, suggesting it is mechanistically nonoverlapping with IM-induced apoptosis. (lu.se)
Regulation2
- This Non-receptor tyrosine-protein kinase plays an important role in the regulation of cell growth, differentiation, migration and immune response. (wikipedia.org)
- Regulation of MT dynamics via direct binding of an Abl family kinase. (nih.gov)
Differentiation1
- Src and other Src family protein tyrosine kinases are proto-oncogenes that play key roles in regulating cell growth and differentiation. (rndsystems.com)
Locus1
- Corticosterone increases protein tyrosine kinase activity in the locus coeruleus and other monoaminergic nuclei of rat brain. (aspetjournals.org)
Phosphoinositide1
- These proteins are phosphorylated by phosphoinositide 3-kinase (PI3K). (senescence.info)
Human3
- Phosphorylation at Y419 of human Src up-regulates kinase activity, while phosphorylation at Y530 inactivates Src. (rndsystems.com)
- Western Blot: PAG3 Antibody [NBP2-24614] - Analysis of ASAP2 in human brain lysate using 1) preimmune sera at 1:5000 and 2) protein A purified this antibody. (novusbio.com)
- Differentially expressed candidate genes for ageing previously identified in the human blood transcriptome up-regulated in PP cows were mainly associated with T-cell function ( CCR7 , CD27 , IL7R , CAMK4 , CD28 ), mitochondrial ribosomal proteins ( MRPS27 , MRPS9 , MRPS31 ), and DNA replication and repair ( WRN ). (biomedcentral.com)
Stimulation1
- The present work has an objective to evaluate the involvement of PTK activity on neutrophil population in the peripheral blood upon stimulation with G-CSF plus IL-15 in leukemic animal. (journalcra.com)
Cell8
- Tyrosine-Kinase CSK is mainly present in the cytoplasm, but also found in lipid rafts making cell-cell junction. (wikipedia.org)
- Genes whose protein products can directly or indirectly prevent cell division or lead to cell death. (cancerquest.org)
- The Wee1 class of protein-tyrosine kinase has an important role in cell cycle control. (berkeley.edu)
- We investigated control mechanisms that regulate the activity, localization, and stability of Wee1, especially the bud neck-localized protein kinase Hsl1 and its more distant paralogs (Gin4 and Kcc4), in particular their recruitment to septin filaments, which assemble at the presumptive site of cell division. (berkeley.edu)
- We also studied the roles of other classes of protein kinases (Cla4) and additional post-translational modifications (SUMOylation) in septin complex assembly, formation of different septin-based supramolecular ensembles, disassembly of septin-containing structures, and the function of septin organization in the events required for cell division and membrane septation during cytokinesis. (berkeley.edu)
- Understanding the mechanisms that regulate signaling by these kinases should uncover new ways to inhibit cancer cell growth. (cancer.gov)
- p210-breakpoint peptide-specific CD4+ T cells isolated from vaccinated patients were found to be either perforin+ or CD25+/Foxp3+: in both cases they exerted direct cytotoxic activity against a CML cell line [ 8 ]. (hindawi.com)
- As a biologically important example we have studied the complex formed by cyclins and cyclin-dependent kinases (CDKs), which play an essential role in the control of the eukaryotic cell cycle. (lu.se)
Family4
- CSK acts by suppressing the activity of the Src family of protein kinases by phosphorylation of Src family members at a conserved C-terminal tail site in Src. (wikipedia.org)
- Upon phosphorylation by other kinases, Src-family members engage in intramolecular interactions between the phosphotyrosine tail and the SH2 domain that result in an inactive conformation. (wikipedia.org)
- Src family activity is regulated by tyrosine phosphorylation at two sites with opposing effects. (rndsystems.com)
- The ROR2 protein is part of a family of proteins known as receptor tyrosine kinases (RTKs), which play a role in chemical signaling within cells. (medlineplus.gov)
Interactions2
- No yeast two-hybrid interactions found for this protein. (yeastrc.org)
- Furthermore, the deleterious aftereffect of missense mutations can occur not merely from immediate disruption of CAPN3 function(s), but additionally from disruption from the protein's structural integrity, that could affect its intra or intermolecular protein lead and interactions to decreased stability or altered localization. (exposed-skin-care.net)