Searched for: data_source:CELL_MAP [All Organisms, All Data Sources]

Summary:  TNF alpha is a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily.It signals through two distinct cell surface receptors, TNFR1 and TNFR2. NFKB is a transcription regulator that is activated by various intra and extra cellular stimuli including cytokines like TNF alpha. The TNF alpha induced NFKB activity involves the five mammalian NF-kappaB/Rel proteins that have been cloned and characterized, so far that is : c-Rel, NF-kappaB1 (p50/p105), NF-kappaB2 (p52/p100), RelA/p65, RelB. In the absence of TNF alpha stimulation, NF-kappaB is associated with the inhibitor IkappaB in the cytoplasm.TNF-induced activation of NF-kB largely relies on phosphorylation dependent ubiquitination and degradation of inhibitor of kappa B (IkB) proteins. The inhibitor of kappa B kinase (IKK) complex, a multiprotein kinase complex is responsible for the TNF alpha induced phosphorylation of IkB. The free NF-kappaB translocates to the nucleus and induces expression of certain genes. TRADD adaptor molecule interacts with TNFR1 and recruits the additional adaptor proteins like RIP, TRAF2, and FADD, which in turn recruit additional key components to TNFR1 responsible for initiating downstream events and mediating programmed cell death signaling and NF-kappaB activation. This pathway is involved in the regulation of a wide spectrum of biological processes including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation.

Summary:  Transforming growth factor beta (TGF-beta) is a multi functional cytokine which binds to the heteromeric complexes of TGF-beta type I and type II serine/threonine kinase receptors and activates TGF-beta receptor complex, which phosphorylates and activates SMAD2 and SMAD3, then associate with Smad4 and migrate into the nucleus and regulate expression of different target genes.Key players of TGF-beta receptor signal transduction pathway include TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, SMADs, SnoN, SARA, SKI, DAB, TRAP, TAK1 SMIF, E2F4, E2F5, RBL1, RBL2, RB1, TFDP1, TFDP2, SMURF1, SMURF2, P300, CBP, JUN.SMAD mediated TGF-beta receptor pathway regulates various cellular and physiological processes such as proliferation, differentiation, growth, migration, myelination, cell cycle arrest, apoptosis and development.

Summary:  Hedgehogs are secreted proteins namely Sonic(SHH),Desert(DHH),Indian(IHH) found in mammals. After secretion, the diffusion of all three Hh ligands is limited to binding to transmembrane receptors such as HIP1,PATCHED1 (PTCH1),and PATCHED2 (PTCH2). In absence of ligand, Patched receptors block the function of another transmembrane protein, Smoothened (SMO) and this inhibition is relieved following ligand binding. SMO becomes active and intiates signalling cascade that results in the activation of GLI transcription factors which translocate to nucleus upon ligand binding and control target genes expression. Hh signalling regulates transcription of genes such as HHIP, PTCH, CCND2, CCNE1 and FOXG1A that are important for various cellular processes. Hedgehog pathway is essential for cell cycle regulation and embryogenesis.

Summary:  Tyrosine kinase is a transmembrane receptor that is expressed in a variety of different tissues and mediates pleiotropic biological effects through its ligand stem cell factor (SCF). Different kinases (like PI3K, PRKCB, Tec, Lyn) and adapter molecules (DOK1, SOCS1, SOCS6) are involved in Kit pathway. KIT pathway regulates gene expression of various types of proteins like transcription factors (MYB, MYC), ligands and receptors (TNF, Interleukins), adapter molecules (SOCS1, SOCS6). Many of them are involved in the KIT pathway itself.KIT pathway controls various cell processes like Cell Proliferation, Apoptosis, Chemotaxis.

Summary:  The integrins are cell membrane receptors composed of alpha and beta subunits. There are about 18 alpha subunits and 8 beta subunits.Integrins alpha6 and beta 4 heterodimerises to form the active receptor complex. Alpha6Beta4 are mainly involved with hemidesmosomes formation, cell adhesion and cell attachments. Many cytoskeletal proteins like keratins and Bullous pemphigoid antigen (BPAG) are associated with Alpha6beta4.They also associate with other receptors like Epidermal Growth factor receptor(EGFR), macrophage stimulating factor receptors. The vital ligands are Laminins, Kalinins. Various kinases (like MEKs, ERKs, PKCs, YES, FYN) and adapter molecules like (GRBs) are involved in this pathway. Alpha6beta4 modulate processes as diverse as cell proliferation, differentiation, apoptosis, migration and tissue morphogenesis.

Summary:  Notch is a cell-surface receptor that is activated by contact with membrane-bound ligands on neighboring cells. Extracellular regions of the Notch receptors (Notch1, Notch2, Notch3, Notch4) interact with ligands such as Dll1, Dll4, JAG1 and JAG2 to activate the Notch cascade. Interaction of Notch with its ligands triggers proteolytic processing of Notch, first by a metalloproteinase, and then by the gamma secretase complex (including presenilins). The cytoplasmic domain of Notch is released from the plasma membrane by proteolysis, and it then travels to the nucleus. In the nucleus, Notch interacts with CBF-1, CBF-3,MAML1, MAMl2, MAML3, FBXW7 to regulate the transcription of downstream genes. HES and HERP family proteins are the primary effectors of the Notch signaling pathway. Notch pathway controls various celular processes such as differentiation, apoptosis, transport, cell cycle and development.

Summary:  The Epidermal growth factor (EGF) signals through the epidermal growth factor (EGF) receptor (EGFR) family composed of four receptor tyrosine kinases (RTKs) designated EGFR, ErbB2 (also known as HER2 or neu), ErbB3 (HER3), and ErbB4 (HER4).In EGFR1 pathway, it includes interactions of EGF-EGFR only.Binding of EGF to the extracellular domain of these RTKs leads to receptor dimerization, activation of the intrinsic protein tyrosine kinase (PTK) activity, tyrosine autophosphorylation, and recruitment of various signaling proteins to the receptor. .Tyrosine phosphorylation of the EGFR leads to the recruitment of various signaling proteins, including the adaptor proteins Grb2 , Nck, phospholipase C gamma , Shc and other molecules. .The EGF receptor activates RAS and the MAP kinase pathways, ultimately causing phosphorylation of transcription factors such as c-Fos, c-Jun, ELK-1 . The STAT transcription factors are also activated by JAK kinases in response to EGF. .This pathway is involved in the regulation of a wide spectrum of biological processes including cell proliferation, apoptosis, cell cycle etc.

Summary:  Androgen receptor is a member of the steriod hormone family.Androgen pathway is responsible for mediating the physiologial effects of androgens by binidng to specific DNA sequences that infulence trancription of androgen responsive genes. Androgen receptor pathway regulates the expression of several genes that are involved in various biological processes such as glycolysis,cell growth and maintenance,cell development,lipid metabolism,p53 activity,apoptosis and hormone mediated signaling. Mutations in androgen receptor gene confers genetic predisposition to prostate cancer.

Summary:  WNT family members are secreted glycoproteins which bind to Frizzleds and LRPs, the cell surface receptors as well as with other downstream signaling components, like DVL, FRATs, casein kinases, AXINs etc. Under WNT stimulation, there are three sub pathways that have been reported such as Beta-catenin, Planar cell polarity and Calcium dependent. Canonical WNT/Beta-catenin pathway (WNT/Beta-catenin): Axin and APC bind to both beta-catenin and GSK3, to facilitate phosphorylation of beta-catenin by GSK-3beta. Phosphorylated beta-catenin is then degraded in proteasomes by the ubiquitination machinery (PMID: 15203747). Unphosphorylated beta-catenin first accumulates in the cytoplasm and then translocates to the nucleus where it associates with other transcription factors such as TCF3, TCF4 and LEF1 and regulate the expression of different target genes such as CDH1, CCND1, DKK1, JUN, MYC, FRA1, BTRC, CDX1. Non-canonical planar cell polarity pathway: WNT11 and WNT5A activate the WNT/JNK pathway which regulate planar cell polarity pathway. FZDs and DVLs are important components of this pathway. WNT/calcium signaling pathway: WNTs, FZDs and DVL2 activate calcium sensitive enzymes like PKCs and CAM kinase II to regulate cellular processes like cell migration, cell development and differentiation (PMID: 14766423). FRPs and DKKs are known to antagonize WNT signaling pathway.In general, activation of WNT pathway control various cellular processes like proliferation, development, adhesion, cell cycle, sex differentiation, migration, differentiation, polarity and apoptosis.

Summary:  Id Proteins are members of the basic HLH(helix-loop-helix ) family of transcription factors but lack a DNA binding domain. The Id family of proteins comprises of 4 members designated Id1-Id4.They have been demonstrated to bind the ubiquitously expressed bHLH E-proteins or cell lineage-restricted bHLH transcription factors, leading to inhibition of lineage-specific gene expression and differentiation.Hence, the name Id refers to both inhibition of differentiation and inhibition of DNA binding.Id proteins have been implicated in regulating a variety of cellular processes, including cellular growth, senescence, differentiation, apoptosis, angiogenesis, and neoplastic transformation.