Search results for CD44

Showing 17 results out of 27

×

Species

Types

Compartments

Reaction types

Search properties

Species

Types

Compartments

Reaction types

Search properties

Protein (2 results from a total of 2)

Identifier: R-HSA-1031688
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: CD44: P16070
Identifier: R-HSA-6804776
Species: Homo sapiens
Compartment: secretory granule membrane
Primary external reference: UniProt: CD44: P16070

Interactor (1 results from a total of 1)

Identifier: EBI-6620336
Species: Homo sapiens
Primary external reference: IntAct: EBI-6620336

DNA Sequence (1 results from a total of 1)

Identifier: R-HSA-9034216
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: ENSEMBL: ENSG00000026508

RNA Sequence (4 results from a total of 5)

Identifier: R-HSA-428370
Species: Homo sapiens
Compartment: cytosol
Primary external reference: ENSEMBL: CD44 mRNA isoform 203: ENST00000278386
Identifier: R-HSA-428290
Species: Homo sapiens
Compartment: cytosol
Primary external reference: ENSEMBL: CD44 mRNA isoform 205: ENST00000352818
Identifier: R-HSA-428379
Species: Homo sapiens
Compartment: cytosol
Primary external reference: ENSEMBL: CD44 mRNA isoform 201: ENST00000263398
Identifier: R-HSA-428347
Species: Homo sapiens
Compartment: cytosol
Primary external reference: ENSEMBL: CD44 mRNA isoform 202: ENST00000278385

Reaction (4 results from a total of 13)

Identifier: R-HSA-2752115
Species: Homo sapiens
Compartment: plasma membrane, extracellular region
Osteopontin (SPP1) is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family of proteins (Bellahcène et al. 2008). It is a highly phosphorylated sialoprotein and prominent component of the mineralized extracellular matrices of bones and teeth. It binds multiple integrins including alphaVbeta3, alphaVbeta1 and alphaVbeta5 (Liaw et al. 1995) alpha9beta1 (Smith et al. 1996, Yokosaki et al. 1999), alpha4beta1 (Bayliss et al. 1998) and the receptor CD44 (Weber et al. 1996, Katagiri et al. 1999). The SPP1–CD44 interaction may be important for colorectal cancer progression (Rao et al. 2013).
Identifier: R-HSA-1454791
Species: Homo sapiens
Compartment: plasma membrane, extracellular region
Certain normally extracellular MMPs can transiently localize at the cell periphery in association with adhesion receptors or proteoglycans. ProMMP9, MMP9, MMP2 and MMP7 (Ahmed et al. 2002, Samanna et al. 2006, Yu et al. 2002) localize at the cell membrane with the single-pass transmembrane glycoprotein CD44, known to be involved in hyaluronan-cell interactions, lymphocyte homing and cell adhesion (Toole 1990). Membrane-associated MMP7 can bring about the shedding of several membrane proteins such as epidermal growth factor (EGF), soluble Fas ligand (FasL), E-cadherin and TNF-alpha from their membrane-bound precursors, thereby promoting cancer progression (Li et al. 2006). MMP9 is able to cleave CD44, inhibiting cell migration and reducing the malignant potential of tumour cells (Chetty et al. 2012).
Identifier: R-HSA-2160906
Species: Homo sapiens
Compartment: lysosomal lumen, plasma membrane
The smallest fragments HYAL2 can generate are 20kDa (approximately 50 disaccharide unit) HA fragments. These fragments are internalized and delivered to lysosomes (Knudson et al. 2002, Erickson & Stern 2012) where another hyalurindase, HYAL1, can degrade them further.
Identifier: R-HSA-2160915
Species: Homo sapiens
Compartment: plasma membrane, extracellular region
HA receptors mediate the uptake of HA into cells. CD44 consists of four functional domains, the extracellular distal domain being the HA-binding region (Culty et al. 1990, Asher & Bignami 1992). The receptor for hyaluronan mediated motility (RHAMM, also called HMMR) can bind HA but not heparin or chondroitin sulfate (Assmann et al. 1998, Wang et al. 1996). Lymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE1) removes HA from the lymphatic system (Banerji et al. 1999). It is present mainly on lymphatic endothelial cells but also in liver sinusoids. Hyaluronan receptor for endocytosis (HARE, stabilin-2, STAB2) binds to and mediates endocytosis of HA (Harris et al. 2007, Harris et al. 2004). HARE can also bind other glycosaminoglycans such as heparin (Harris et al. 2008).
High molecular weight HA is tethered to the cell surface by HA receptors and the GPI-linked hyaluronidase 2 (HYAL2) to form a HA:HAR:HYAL2 complex in the plasma membrane that localizes to caveolae (invaginations of the plasma membrane composed of cholesterol and gangliosides and rich in caveolin and flotillin).

Complex (2 results from a total of 2)

Identifier: R-HSA-2752110
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-2559499
Species: Homo sapiens
Compartment: plasma membrane

Pathway (3 results from a total of 3)

Identifier: R-HSA-6806942
Species: Homo sapiens
Hepatocyte growth factor (HGF), the ligand for MET receptor tyrosine kinase (RTK), is secreted into the extracellular matrix (ECM) as an inactive single chain precursor (pro-HGF). The biologically active HGF is the heterodimer of alpha and beta chains that are produced via proteolytic cleavage of pro-HGF by the plasma membrane bound serine protease Hepsin (HPN) (Kirchhofer et al. 2005, Owen et al. 2010) or the ECM-associated serine protease Hepatocyte growth factor activator (HGFAC, commonly known as HGFA) (Shia et al. 2005). HGF binds to the extracellular SEMA and PSI domains of MET RTK, inducing a conformational change that enables MET dimerization or oligomerization (Kirchhofer et al. 2004, Stamos et al. 2004, Hays and Watowich 2004, Gherardi et al. 2006). MET dimers trans-autophosphorylate on tyrosine residues in the activation loop, leading to increased kinase activity, and on tyrosine residues at the cytoplasmic tail that serve as docking sites for adapter proteins involved in MET signal transduction (Ferracini et al. 1991, Longati et al. 1994, Rodrigues and Park 1994, Ponzetto et al. 1994).
CD44v6 was implicated as a MET co-receptor, but its role has been disputed (Orian-Rousseau et al. 2002, Dortet et al. 2010, Olaku et al. 2011, Hasenauer et al. 2013, Elliot et al. 2014).
Identifier: R-HSA-8875360
Species: Homo sapiens
InlB, a cell wall protein of Listeria monocytogenes, binds MET receptor, acting as an HGF agonist (Shen et al. 2000, Veiga and Cossart 2005). Listeria monocytogenes InlB proteins dimerize through their leucine-rich repeat regions (LRRs), promoting dimerization of MET receptors that they are bound to (Ferraris et al. 2010). InlB-induced MET receptor dimerization is followed by MET trans-autophosphorylation and activation of downstream RAS/RAF/MAPK signaling and PI3K/AKT signaling (Niemann et al. 2007, Ferraris et al. 2010). InlB-bound phosphorylated MET receptor recruits the E3 ubiquitin ligase CBL through GRB2. CBL-mediated monoubiquitination of InlB-bound MET promotes endocytosis and entry of Listeria monocytogenes to host cells (Veiga and Cossart 2005). CIN85 is necessary for endocytosis-mediated entry of Listeria monocytogenes triggered by CBL-mediated monoubiquitination of MET (Veiga and Cossart 2005). Proteins involved in clathrin-mediated endocytosis EPS15 and HGS (Hrs) are both necessary for CBL and MET-mediated entry of Listeria monocytogenes into host cells (Veiga and Cossart 2005).
A potential coreceptor role of CD44 in InlB-mediated MET activation is contradictory (Jung et al. 2009, Dortet et al. 2010).
Identifier: R-HSA-1474244
Species: Homo sapiens
The extracellular matrix is a component of all mammalian tissues, a network consisting largely of the fibrous proteins collagen, elastin and associated-microfibrils, fibronectin and laminins embedded in a viscoelastic gel of anionic proteoglycan polymers. It performs many functions in addition to its structural role; as a major component of the cellular microenvironment it influences cell behaviours such as proliferation, adhesion and migration, and regulates cell differentiation and death (Hynes 2009).

ECM composition is highly heterogeneous and dynamic, being constantly remodeled (Frantz et al. 2010) and modulated, largely by matrix metalloproteinases (MMPs) and growth factors that bind to the ECM influencing the synthesis, crosslinking and degradation of ECM components (Hynes 2009). ECM remodeling is involved in the regulation of cell differentiation processes such as the establishment and maintenance of stem cell niches, branching morphogenesis, angiogenesis, bone remodeling, and wound repair. Redundant mechanisms modulate the expression and function of ECM modifying enzymes. Abnormal ECM dynamics can lead to deregulated cell proliferation and invasion, failure of cell death, and loss of cell differentiation, resulting in congenital defects and pathological processes including tissue fibrosis and cancer.

Collagen is the most abundant fibrous protein within the ECM constituting up to 30% of total protein in multicellular animals. Collagen provides tensile strength. It associates with elastic fibres, composed of elastin and fibrillin microfibrils, which give tissues the ability to recover after stretching. Other ECM proteins such as fibronectin, laminins, and matricellular proteins participate as connectors or linking proteins (Daley et al. 2008).

Chondroitin sulfate, dermatan sulfate and keratan sulfate proteoglycans are structural components associated with collagen fibrils (Scott & Haigh 1985; Scott & Orford 1981), serving to tether the fibril to the surrounding matrix. Decorin belongs to the small leucine-rich repeat proteoglycan family (SLRPs) which also includes biglycan, fibromodulin, lumican and asporin. All appear to be involved in collagen fibril formation and matrix assembly (Ameye & Young 2002).

ECM proteins such as osteonectin (SPARC), osteopontin and thrombospondins -1 and -2, collectively referred to as matricellular proteins (reviewed in Mosher & Adams 2012) appear to modulate cell-matrix interactions. In general they induce de-adhesion, characterized by disruption of focal adhesions and a reorganization of actin stress fibers (Bornstein 2009). Thrombospondin (TS)-1 and -2 bind MMP2. The resulting complex is endocytosed by the low-density lipoprotein receptor-related protein (LRP), clearing MMP2 from the ECM (Yang et al. 2001).

Osteopontin (SPP1, bone sialoprotein-1) interacts with collagen and fibronectin (Mukherjee et al. 1995). It also contains several cell adhesive domains that interact with integrins and CD44.

Aggrecan is the predominant ECM proteoglycan in cartilage (Hardingham & Fosang 1992). Its relatives include versican, neurocan and brevican (Iozzo 1998). In articular cartilage the major non-fibrous macromolecules are aggrecan, hyaluronan and hyaluronan and proteoglycan link protein 1 (HAPLN1). The high negative charge density of these molecules leads to the binding of large amounts of water (Bruckner 2006). Hyaluronan is bound by several large proteoglycans proteoglycans belonging to the hyalectan family that form high-molecular weight aggregates (Roughley 2006), accounting for the turgid nature of cartilage.

The most significant enzymes in ECM remodeling are the Matrix Metalloproteinase (MMP) and A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) families (Cawston & Young 2010). Other notable ECM degrading enzymes include plasmin and cathepsin G. Many ECM proteinases are initially present as precursors, activated by proteolytic processing. MMP precursors include an amino prodomain which masks the catalytic Zn-binding motif (Page-McCawet al. 2007). This can be removed by other proteinases, often other MMPs. ECM proteinases can be inactivated by degradation, or blocked by inhibitors. Some of these inhibitors, including alpha2-macroglobulin, alpha1-proteinase inhibitor, and alpha1-chymotrypsin can inhibit a large variety of proteinases (Woessner & Nagase 2000). The tissue inhibitors of metalloproteinases (TIMPs) are potent MMP inhibitors (Brew & Nagase 2010).
Cite Us!