Acronyms for insulin signaling proteins

The following are acronyms/explanations of key proteins involved in insulin- induced metabolic signaling, glucose transport and growth.

  • 14-3-3 proteins: bind motifs that contain a phosphorylated serine or threonine residue; the name 14-3-3 refers to the particular elution position on DEAE-cellulose chromatography (14th fraction of a brain homogenate) and migration pattern (position 3.3) after starch-gel electrophoresis.
  • Akt: a protein Ser/Thr kinase (also referred to as PKB). Akt is a human homologue of the retroviral oncogene v-Akt present in a transforming retrovirus isolated from the Ak mouse strain, a mouse that developed spontaneous thymic lymphomas. The "t" stands for ‘thymoma’.
  • aPKC: atypical protein kinase C, a Ser/Thr protein kinase
  • ARF6: ADP-ribosylation factor 6 (ARF6) is a member of the ADP ribosylation factor family of GTP-binding proteins specifically implicated in endocytosis of plasma membrane proteins and also, to a lesser extent, plasma membrane protein recycling.
  • AS160: Akt substrate 160, a 160 kDa RabGAP protein (also known as TBC1D4)
  • BAD: a pro-apoptotic member of the Bcl-2 family
  • CamKII: Ca2+/calmodulin-dependent protein kinase II is a Ser/Thr protein kinase that is regulated by the Ca2+/calmodulin complex.
  • CDC42: a plasma membrane-associated small GTPase involved in epithelial cell polarization processes.
  • Complexins: a family of proteins that compete with SNAP for SNARE binding. They are enriched in neurons where they colocalize with syntaxin-1 and SNAP-25 and regulate the sequential interactions of SNAP and synaptotagmin with the SNARE complex during exocytosis. They bind weakly to syntaxin-1 alone and not at all to synaptobrevin and SNAP-25, but strongly to the SNARE complex composed of these three molecules.
  • DENND4C: a 1673 residue cytoplasmic vesicle membrane-associated guanine nucleotide exchange factor (GEF) that activates RAB10, thereby stimulating the delivery of GLUT4 glucose transporter-enriched vesicles to the plasma membrane in response to insulin. Six isoforms of the human protein are produced by alternative splicing.
  • DOC2b: double C2-like domain beta
  • ERK1: extracellular signal-regulated kinase 1, a Ser/Thr protein kinase; equivalent to MAP3K and Raf
  • ERK2: extracellular signal-regulated kinase 2, a Ser/Thr protein kinase; equivalent to MAPK1
  • ESYT1: extended synaptotagmin-like protein 1
  • Exocyst: an octameric protein complex involved in vesicle trafficking, specifically the tethering and spatial targeting of post-Golgi vesicles to the plasma membrane prior to vesicle fusion.
  • FOXO: forkhead box, O subclass transcription factors regulating expression of gluconeogenic and other genes
  • GAPs: GTPase-activating proteins (GAPs) which along with GEFs regulate the activity of small guanine nucleotide-binding (G) proteins to control cellular functions. In general, GEFs turn on signaling by catalyzing the exchange from G-protein-bound GDP to GTP, whereas GAPs terminate signaling by inducing GTP hydrolysis. GEFs and GAPs are multidomain proteins that are regulated by extracellular signals and localized cues that control cellular events in time and space.
  • GEFs: Guanine nucleotide exchange factors, multidomain proteins which along with GTPase-activating proteins (GAPs) regulate the activity of small guanine nucleotide-binding (G) proteins to control cellular functions.
  • GGA: Golgi-localized, gamma-ear containing, ADP-ribosylation factor binding family of multidomain coat proteins that occupy a central position in the trafficking of the mannose 6-phosphate receptors and other cargo molecules from the trans-Golgi network to the endosome/lysosome system.
  • GLUT1 to 4: glucose transporter 1 to 4
  • Grb2: growth factor receptor binding protein 2
  • GSK-3: glucose synthase kinase 3
  • JNKs: c-Jun N-terminal kinases; originally identified as kinases that bind and phosphorylate c-Jun on Ser-63 and Ser-73 within its transcriptional activation domain. Belong to the mitogen activated protein kinase (MAPK) family.
  • IR – insulin receptor
  • IRAP - insulin-responsive aminopeptidase; a leucyl/cystinyl aminopeptidase. A type II membrane protein and secreted. Resides in intracellular vesicles together with GLUT4 and can then translocate to the cell surface in response to insulin and/or oxytocin.. Degrades peptide hormones such as oxytocin, vasopressin and angiotensin III, and plays a role in maintaining homeostasis during pregnancy. May be involved in the inactivation of neuronal peptides in the brain. Cleaves Met-enkephalin and dynorphin. Binds angiotensin IV and may be the angiotensin IV receptor in the brain. Three alternatively spliced isoforms have been described. Note: This description may include information from UniProtKB.
  • IRS1 to 4: insulin receptor substrates 1 to 4
  • MAPK1: mitogen activated protein kinase 1, a Ser/Thr protein kinase (also termed ERK2)
  • MAP2K: mitogen activated protein kinase kinase, a Ser/Thr protein kinase that activates mitogen activated protein kinase (MAPK); also known as MEK.
  • MEK: MAPK/ERK kinase, a dual specificiity Tyr/Thr kinase, also known as MAP2K
  • mTORC2: mammalian target of rapamycin complex2, a Ser/Thr protein kinase
  • Munc13: mammalian homologue of unc-13; essential for exocytosis.
  • Munc18a and Munc18c: mammalian uncoordinated-18a and -18c; mammalian homologues of unc-18 a member of the Sec1/Munc18-like (SM) family
  • MYO: myosin motors
  • NSF: N-ethylmaleimide sensitive factor, is an ATPase involved in vesicle transport
  • PDK1: phosphoinositide-dependent kinase-1, a Ser/Thr protein kinase
  • PHLPP: PH domain leucine-rich repeat protein phosphatase, specifically dephosphorylates the hydrophobic motif of Akt (Ser473 in Akt1)
  • PI3K: phosphotidylinositol 3-kinase, phosphorylates phosphoinositides on the 3 position.
  • PKB: protein kinase B, a Ser/Thr protein kinase also referred to as Akt
  • PT1B: phosphotyrosine phosphatase 1B
  • PTB domain: phosphotyrosine binding domain
  • Rab: small GTPase. Rabs are the largest member of the Ras superfamily of small GTPases. They oscilate between an inactive GDP-bound conformation and an active GTP-bound state that is tethered to the plasma membrane via a C-terminal prenylation site on conserved cysteine residues. Rabs regulate various aspects of membrane trafficking by binding specific effector molecules when in their activated (GTP-bound) state. See Khan AR, Oligomerization of rab/effector complexes in the regulation of vesicle trafficking. Prog Mol Biol Transl Sci. 2013, 117:579-614 for a detailed review of Rab/effector complexes and vesicle trafficking.
  • Raf: cellular homologue of oncogene products from 3611 murine sarcoma virus and Mill Hill 2 avian leukemia virus; a Ser/Thr protein kinase; also known as MAP kinase kinase kinase (MAP3K) and ERK1.
  • Ras: is a small GTPase, gets its name from rat sarcoma
  • Rheb: Ras homologue enriched in brain, small GTPase
  • Rho: a family of small (~21 kDa) signaling G-proteins GTPases); shown to regulate many aspects of intracellular actin dynamics, and found in all eukaryotic organisms including yeasts and some plants. All G proteins are "molecular switches", and Rho proteins play a role in organelle development, cytoskeletal dynamics, cell movement, and other common cellular functions
  • SH2: Src-homology-2 domain, binds 4 residue phosphotyrosine motifs pYXXX
  • Shc: SH2 and CH1 (collagen homology, proline-rich) domain containing protein
  • SM proteins: Sec1/Munc18-like proteins; all intracellular membrane fusion except for mitochondrial fusion is driven by SNARE and SM proteins
  • SNAP: soluble NSF attachment protein; highly conserved protein that participates in intracellular membrane fusion and vesicular trafficking.
  • SNAP-23: synaptosomal-associated protein 23, a target SNARE protein involved in GLUT4 translocation. It is unrelated to SNAP, the soluble NSF attachment protein.
  • SNAP-25: synaptosomal-associated protein 25, a target SNARE protein involved in synaptic transmission. It is unrelated to SNAP, the soluble NSF attachment protein.
  • Snapin: also termed SNAPAP for SNARE-associated protein
  • SNARE: Soluble NSF attachment protein receptor
  • SNAREpins: trans-SNARE complexes linking two membranes, leading to spontaneous fusion of the docked membranes at physiological temperature. SNAREpins are the minimal machinery for cellular membrane fusion.
  • SOS: son of sevenless protein, a guanine nucleotide exchange factor that binds to Grb2 and activates Ras, a small GTPase, by promoting the exchange of GDP with GTP.
  • Syntaxin4: a target SNARE protein involved in GLUT4 translocation
  • Synaptobrevins: also termed vesicle associated membrane proteins (VAMPs); v-SNAREs involved in fusion of vesicles to the plasma membrane.
  • Synaptotagmins: a family of proteins with an N-terminal transmembrane domain and two cytoplasmic C2 domains. Many C2 domains mediate calcium-dependent binding to negatively charged membranes. Synaptotagmin-1 is localized to synaptic vesicles and is the trigger for their calcium-induced exocytosis. The two C2 domains of synaptotagmin-1 insert into the membrane upon calcium binding. (See Synaptotagmin, the calcium sensor for exocytosis.)
  • TBC1 domain: Tre-2/Bub2/Cdc16 domain originally identified as a conserved domain among the tre-2 oncogene product and the yeast cell cycle regulators Bub2 and Cdc16.
  • TBC1D4: TBC1 domain family member 4, a 160 kDa RabGAP protein (also known as AS160).
  • TBC1D13: a TBC1domain family member, a potent suppressor of GLUT4 translocation. Interacts with Rab10 and Rab1 in a GTP-dependent manner but it does not display GAP activity toward either of these Rabs. Rather, TBC1D13 stimulates Rab35 GTP hydrolysis in vitro and in vivo.
  • TC10: a Rho family GTPase, that has been shown to play an important role in the exocytosis of GLUT4 and other proteins, primarily by tethering the vesicles at the plasma membrane.
  • TGN: trans-Golgi network, where proteins are sorted for transport to the endosomes, plasma membrane, preceding Golgi cisternae, and endoplasmic reticulum.
  • t-SNAREs: target SNAREs, located in the membranes of target compartments.
  • VAMP-1 and -2: vesicle associated membrane proteins 1 and 2, vesicle SNARE proteins (v-SNAREs) involved in fusion of vesicles to the plasma membrane. Also called synaptobrevins.
  • v-SNAREs: small integral membrane proteins of secretory vesicles with moleculae weight of 18 kilodalton (kDa) that are part of the vesicle-associated membrane protein (VAMP) family.

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