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2.8 EGF receptor and the Ras protein
 
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The EGF receptor functions as a tyrosine kinase (TK) EGF was found to have mitogenic effects when applied to a variety of epithelial cell types. EGF was able to bind to the surfaces of the cells whose growth it stimulated; other cells to which EGF was unable to bind were unresponsive to its mitogenic effects. An EGF receptor protein can specifically recognize EGF bind to it, and inform the cell interior The EGF receptor The cytoplasmic domain revealed a clear sequence similarity with the already-known sequence of the Src protein Signal activated EGF leads to the Src-like kinase in its cytoplasmic domain becoming activated to phosphorylate tyrosines on certain cytoplasmic proteins thereby causes a cell to proliferate. There are many receptor tyrosine kinases Subsequent sequencing efforts revealed overall sequence similarities among a variety of tyrosine kinases, many of which can function as oncoproteins. Truncated versions of the EGF receptor are found in a number of human tumor cell types. A variety of growth factor receptors that are configured much like the EGF receptor have been found in human tumors to be overexpressed or synthesized in a structurally altered form Autocrine signaling loops Some human cancers produce as many as three distinct growth factors Eg tumor growth factor-a, TGF-a stem cell factor; or SCF; insulin-like growth factor; or IGF At the same time express the receptors for these three ligands, thereby establishing three autocrine signaling loops simultaneously. In normal tissues, the proliferation of individual cells almost always depends on signals received from other cells Growth Factor activated receptors tyrosine kinase signal to ras “Ras” carry covalently attached lipid tails, composed of farnesyl, palmitoyl, and is anchored to cytoplasmic membranes the Ras molecule seemed to behave like a light switch that automatically turns itself off after a certain predetermined time. Ras switching Ras was found to bind a GDP molecule when in its quiescent, inactive state to jettison its bound GDP after receiving some stimulatory signal from upstream in a signaling cascade to acquire a GTP molecule in place of the recently evicted GDP to shift into an activated, signal-emitting configuration while binding this GTP to cleave this GTP after a short period by using its own intrinsic GTPase function Signalling to “Ras” Mitogenic signals, transduced in some way by tyrosine kinase receptors, activated a guanine nucleotide exchange factor (GEF) for Ras. Ras receives signals from upstream in a signalling cascade subsequently passes these signals on to a downstream targets How does “Ras” signal? Ras can operate as an oncoprotein: Typically mutations strike either the 12th or the 61st codon of the reading frame of the ras gene Rather than sending out short, carefully rationed pulses of growth-stimulating signals, the oncoprotein emits these signals for a long, indefinite period of time. Thereby flooding the cell with these signals Why do point mutations Activate oncogenes Large-scale alterations of the ras proto-oncogenes, such as deletions, are clearly not productive for cancer, they result in the elimination of Ras protein function The vast majority of point mutations striking ras protooncogenes yield mutant Ras proteins that have lost rather than gained the ability to emit growth-stimulatory signals. Only when the signal-emitting powers of Ras are left intact and its GTPase negative-feedback mechanism is inactivated does the Ras protein gain increased power to drive cell proliferation and transform the cell. Point mutations in the GTPase domain keep ras active
Views: 3071 Mark Temple
Figure 18.17 Determining the guanine nucleotide exchange properties of EF-Ts
 
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This video describes an experiment that shows that EF-Ts promotes the release of GDP from EF-Tu. This is figure 18.17 from Molecular Biology 5th edition by Robert Weaver. It was made for MCDB 427, a molecular biology course at the University of Michigan.
Views: 85 MCDB 427
Molecular Cloning of Rho Family Guanine Nucleotide Exchange Factors FGD1-5
 
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Student Achievement Day Presentation at Bemidji State University
Views: 130 bawani129
Ran GTPase, GAP, GEF
 
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The dynamic process between the cytosol and the nucleus of how Ran-GDP cycles with Ran-GTP
Views: 1009 kaleidoscopicKT
Alfred Wittinghofer (MPI) Part 1: GTP-binding Proteins as Molecular Switches
 
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https://www.ibiology.org/biochemistry/g-protein/ When a growth factor binds to the plasma membrane of a quiescent cell, an intracellular signaling pathway is activated telling the cell to begin growing. A key molecule in this signaling pathway is the GTP-binding protein, or G-protein, Ras. Ras can act as an on-off switch telling the cell to grow or not. In its inactive form, Ras is bound to GDP while in its active form it is bound to GTP. This exchange of nucleotides is catalysed by guanine nucleotide-exchange-factors (GEFs). The return to the inactive state occurs through the GTPase reaction, which is accelerated by GTPase-activating proteins (GAPs). In Part 1 of his talk, Dr. Wittinghofer explains how solving the three-dimensional structure of Ras, and other G-proteins, allowed him to understand the conserved mechanism by which G-proteins can act as switches. The structure also identified domains unique to each G-protein that provide the specificity for downstream signals.
Views: 33465 iBiology
Medical vocabulary: What does ras Guanine Nucleotide Exchange Factors mean
 
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What does ras Guanine Nucleotide Exchange Factors mean in English?
Views: 15 botcaster inc. bot
02 Oncogenes
 
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A presentation on Cancer Genetics discussing Oncogenes and the Ras signalling protein as an example. Cellular Oncogenes The cell genome is rich source of the genes that drive human cancer The cellular genome has tens of thousands of genes. A large catalog of cellular cancer-causing genes has been assembled. These are called oncogenes and tumor suppressor genes Consider the H-ras gene The oncogene that had been cloned from human bladder carcinoma cells caused transformation of NIH 3T3 cells, while its normal proto-oncogene counterpart (i.e., the normal Hras gene) lacked this ability. A 350-bp segments from the proto-oncogene and oncogene were subjected to DNA sequence analysis. The critical difference was extraordinarily subtle—a single base substitution in which a G (guanosine) residue in the proto-oncogene was replaced by a T (thymidine) in the oncogene. This single base-pair replacement - a point mutation - appeared to be all that was required to convert the normal gene into a potent oncogene The H-ras gene This was the first time that a mutation was discovered in a gene that contributed to the growth of a human cancer. This genetic change arose as a somatic mutation. The importance of Ras proteins in tumors In the 1980s, it was demonstrated that close to 30% of all solid tumors in humans show a mutation in the Ras gene. Certain positions in the Ras protein are particularly sensitive to oncogenic mutations. Replacement of Gly12 in the Ras protein with any of the other natural amino acids (except Pro) leads to an increase in the tumor-transforming potential of Ras protein. RAS a switch protein Structure and Biochemical Properties of Ras Protein The Ras protein is a GTPase the GTP-bound form represents the active, switched-on state the GDP-bound form is the inactive, switched-off state The transition between the active and inactive forms occurs in a unidirectional cycle The Ras activation cycle Ras On… GEF Guanine Exchange Factors Sos protein Is a GEF that provokes nucleotide exchange by G proteins (guanine nucleotide-binding), such as Ras. Ras Off… GAP GTPase Activating Protein GTPase-activating proteins (GAP), increase the rate of GTP hydrolysis of the Ras protein up to 105-fold. reducing the lifetime of the active GTP state. Due to this property, they function as negative regulators of the Ras protein. Cancer Genetics in brief series… by Mark Temple
Views: 4105 Mark Temple
The G Protein (Guanine-nucleotide binding protein)
 
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Baltazar, John Marion Rafael C. Busania, Vince N. A requirement in Bio126 (Animal Morphology and Physiology) submitted to the Faculty of Department of Biology, College of Arts and Sciences, University of the Philippines - Manila.
Views: 18 Vince Busania
[Wikipedia] RhoGEF domain
 
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RhoGEF domain is a structural domain of guanine nucleotide exchange factors for Rho/Rac/Cdc42-like GTPases. It is also called "Dbl-homologous" (DH) domain. https://en.wikipedia.org/wiki/RhoGEF_domain Please support this channel and help me upload more videos. Become one of my Patreons at https://www.patreon.com/user?u=3823907
Views: 24 WikiTubia
Medical vocabulary: What does ras Guanine Nucleotide Exchange Factors mean
 
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What does ras Guanine Nucleotide Exchange Factors mean in English?
Views: 13 botcaster inc. bot
Medical vocabulary: What does Guanine Nucleotide Exchange Factors mean
 
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What does Guanine Nucleotide Exchange Factors mean in English?
Views: 132 botcaster inc. bot
Medical vocabulary: What does Rho Guanine Nucleotide Exchange Factors mean
 
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What does Rho Guanine Nucleotide Exchange Factors mean in English?
Views: 33 botcaster inc. bot
Conformational Change from active (GTP bound) to inactive (GDP bound) state of H-Ras protein.
 
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Watch in 480p for best quality. Ras are a group of small GTPases which are activated by binding of GTP( Guanosine tri phosphate) a process which is facilated by GEF (Guanine nucleotide exchange factor) protein. The Ras which then activates its cellular target for conveying the signal downstream then hydrolyses the bound GTP ( process stimulated by another protein GAP (GTPase Activating Protein) to GDP which the dissociates and the protein returns to its inactive conformation.
Views: 5514 Perunamuusi
Medical vocabulary: What does ral Guanine Nucleotide Exchange Factor mean
 
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What does ral Guanine Nucleotide Exchange Factor mean in English?
Views: 158 botcaster inc. bot
Medical vocabulary: What does rho-Specific Guanine Nucleotide Dissociation Inhibitors mean
 
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What does rho-Specific Guanine Nucleotide Dissociation Inhibitors mean in English?
Gene Music using Protein Sequence of TRIO "TRIO RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR"
 
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Gene Music using Protein Sequence of TRIO "TRIO RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR" Subscribe ➜ https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1 Gene Music Studio - A channel to taste (visually & musically) gene information (particularly protein sequences).
Views: 82 Gene Music Studio
Medical vocabulary: What does Guanine Nucleotide-Releasing Factor 2 mean
 
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What does Guanine Nucleotide-Releasing Factor 2 mean in English?
Medical vocabulary: What does Guanine Nucleotide Dissociation Inhibitors mean
 
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What does Guanine Nucleotide Dissociation Inhibitors mean in English?
Views: 24 botcaster inc. bot
The Universe of GTP-binding proteins: un tema con variationi
 
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Air date: Wednesday, March 25, 2009, 3:00:00 PM Time displayed is Eastern Time, Washington DC Local Category: Wednesday Afternoon Lectures Description: GTP binding (G) proteins of the Ras superfamily cycle between a GDP-bound inactive and a GTP-bound active state. The switch-ON reaction involves the exchange of tightly bound GDP against GTP, while the switch-OFF mechanism involves the enzymatic cleavage of GTP to GDP. The switch function is tightly regulated since those reactions are intrinsically very slow and are stimulated through factors acting in trans. The first reaction is catalysed by guanine nucleotide exchange factors, GEFs, while the second is activated by GTPase-activating proteins called GAPs. The inability of certain of these proteins to be down-regulated or their unregulated activation leads to various forms of diseases including cancer. A lot is known about the structural requirements for the switch function of Ras proteins, the GEF and the GAP reaction, their membrane recruitment and the interaction with effectors. The basic features and mechanistic principles using Ras and G proteins, the structural basis of the molecular switch, how it is activated and how it interacts with downstream effectors, will be presented. Particular attention will be given to the GTPase reaction and its importance for disease formation such as cancer, Retinitis pigmentosa or Parkinson. The NIH Director's Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide. Author: Alfred Wittenhofer Runtime: 00:58:32 Permanent link: http://videocast.nih.gov/launch.asp?14996
Views: 1245 nihvcast
Gene Music using Protein Sequence of ARHGEF1 "RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 1"
 
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Gene Music using Protein Sequence of ARHGEF1 "RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 1" Subscribe ➜ https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1
Gene Music using Protein Sequence of ARHGEF11 "RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 11"
 
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Gene Music using Protein Sequence of ARHGEF11 "RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 11" Subscribe ➜ https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1 Gene Music Studio - A channel to taste (visually & musically) gene information (particularly protein sequences).
Gene Music using Protein Sequence of RAPGEF5 "RAP GUANINE NUCLEOTIDE EXCHANGE FACTOR 5"
 
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Gene Music using Protein Sequence of RAPGEF5 "RAP GUANINE NUCLEOTIDE EXCHANGE FACTOR 5" Subscribe ➜ https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1
Gene Music using Protein Sequence of DEF6 "DEF6 GUANINE NUCLEOTIDE EXCHANGE FACTOR"
 
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Gene Music using Protein Sequence of DEF6 "DEF6 GUANINE NUCLEOTIDE EXCHANGE FACTOR" Subscribe ➜ https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1
Views: 13 Gene Music Studio
Gene Music using Protein Sequence of VAV3 "VAV 3 GUANINE NUCLEOTIDE EXCHANGE FACTOR"
 
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Gene Music using Protein Sequence of VAV3 "VAV 3 GUANINE NUCLEOTIDE EXCHANGE FACTOR" Welcome to Gene Music Studio. Hope you can have a taste (visually & musically) of gene information (particularly protein sequences) in this channel. Subscribe ➜ https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1
Views: 15 Gene Music Studio
Gene Music using Protein Sequence of SERGEF "SECRETION REGULATING GUANINE NUCLEOTIDE EXCHANGE FACTO"
 
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Gene Music using Protein Sequence of SERGEF "SECRETION REGULATING GUANINE NUCLEOTIDE EXCHANGE FACTO"
Gene Music Using Protein Sequence of ARHGEF38 "RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 38"
 
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Gene Music Using Protein Sequence of ARHGEF38 "RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 38"
Views: 18 Gene Music Studio
Gene Music using Protein Sequence of RABGEF1 "RAB GUANINE NUCLEOTIDE EXCHANGE FACTOR (GEF) 1"
 
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Gene Music using Protein Sequence of RABGEF1 "RAB GUANINE NUCLEOTIDE EXCHANGE FACTOR (GEF) 1" Subscribe ➜ https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1
Gene Music using Protein Sequence of ARHGEF2 "RHO/RAC GUANINE NUCLEOTIDE EXCHANGE FACTOR 2"
 
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Gene Music using Protein Sequence of ARHGEF2 "RHO/RAC GUANINE NUCLEOTIDE EXCHANGE FACTOR 2" Subscribe ➜ https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1 Gene Music Studio - A channel to taste (visually & musically) gene information (particularly protein sequences).
Gene Music using Protein Sequence of GNAT1 "GUANINE NUCLEOTIDE BINDING PROTEIN (G PROTEIN), ALPHA T"
 
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Gene Music using Protein Sequence of GNAT1 "GUANINE NUCLEOTIDE BINDING PROTEIN (G PROTEIN), ALPHA T"
Gene Music using Protein Sequence of GNAT2 "GUANINE NUCLEOTIDE BINDING PROTEIN (G PROTEIN), ALPHA T"
 
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Gene Music using Protein Sequence of GNAT2 "GUANINE NUCLEOTIDE BINDING PROTEIN (G PROTEIN), ALPHA T"
Gene Music using Protein Sequence of RIC8B "RIC8 GUANINE NUCLEOTIDE EXCHANGE FACTOR B"
 
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Gene Music using Protein Sequence of RIC8B "RIC8 GUANINE NUCLEOTIDE EXCHANGE FACTOR B" Subscribe ➜ https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1
Gene Music using Protein Sequence of ARHGEF12 "RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR (GEF) 12"
 
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Gene Music using Protein Sequence of ARHGEF12 "RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR (GEF) 12" Subscribe ➜ https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1 Gene Music Studio - A channel to taste (visually & musically) gene information (particularly protein sequences).
Views: 19 Gene Music Studio
Gene Music using Protein Sequence of ARHGEF39 "RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 39"
 
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Gene Music using Protein Sequence of ARHGEF39 "RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 39"
Gene Music using Protein Sequence of ARHGEF5 "RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 5"
 
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Gene Music using Protein Sequence of ARHGEF5 "RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 5" Subscribe ➜ https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1 Gene Music Studio - A channel to taste (visually & musically) gene information (particularly protein sequences).
Gene Music using Protein Sequence of ARHGEF19 "RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 19"
 
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Gene Music using Protein Sequence of ARHGEF19 "RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 19" Subscribe ➜ https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1
Views: 10 Gene Music Studio
Gene Music using Protein Sequence of VAV1 "VAV GUANINE NUCLEOTIDE EXCHANGE FACTOR 1"
 
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Gene Music using Protein Sequence of VAV1 "VAV GUANINE NUCLEOTIDE EXCHANGE FACTOR 1" Subscribe ➜ https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1 Gene Music Studio - A channel to taste (visually & musically) gene information (particularly protein sequences).
Views: 20 Gene Music Studio
Gene Music using Protein Sequence of ARHGEF17 "RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 17"
 
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Gene Music using Protein Sequence of ARHGEF17 "RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 17" Subscribe ➜ https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1 Gene Music Studio - A channel to taste (visually & musically) gene information (particularly protein sequences).
Gene Music using Protein Sequence of ARHGEF7 "RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 7"
 
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Gene Music using Protein Sequence of ARHGEF7 "RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 7" Subscribe ➜ https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1
Gene Music using Protein Sequence of ARHGEF6 "RAC/CDC42 GUANINE NUCLEOTIDE EXCHANGE FACTOR 6"
 
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Gene Music using Protein Sequence of ARHGEF6 "RAC/CDC42 GUANINE NUCLEOTIDE EXCHANGE FACTOR 6" Subscribe ➜ https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1
Views: 10 Gene Music Studio
Gene Music using Protein Sequence of RAPGEF3 "RAP GUANINE NUCLEOTIDE EXCHANGE FACTOR 3"
 
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Gene Music using Protein Sequence of RAPGEF3 "RAP GUANINE NUCLEOTIDE EXCHANGE FACTOR 3" In Gene Music Studio, everyone can get a taste (visually & musically) of gene information (particularly protein sequences). Subscribe ➜ https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1
Gene Music using Protein Sequence of ARHGEF15 "RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 15"
 
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Gene Music using Protein Sequence of ARHGEF15 "RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 15" Subscribe ➜ https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1
Gene Music using Protein Sequence of RIC8A "RIC8 GUANINE NUCLEOTIDE EXCHANGE FACTOR A"
 
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Gene Music using Protein Sequence of RIC8A "RIC8 GUANINE NUCLEOTIDE EXCHANGE FACTOR A" Subscribe ➜ https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1
Gene Music using Protein Sequence of RAPGEF2 "RAP GUANINE NUCLEOTIDE EXCHANGE FACTOR 2"
 
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Gene Music using Protein Sequence of RAPGEF2 "RAP GUANINE NUCLEOTIDE EXCHANGE FACTOR 2" Subscribe ➜ https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1 Gene Music Studio - A channel to taste (visually & musically) gene information (particularly protein sequences).
Gene Music using Protein Sequence of RAPGEFL1 "RAP GUANINE NUCLEOTIDE EXCHANGE FACTOR LIKE 1"
 
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Gene Music using Protein Sequence of RAPGEFL1 "RAP GUANINE NUCLEOTIDE EXCHANGE FACTOR LIKE 1"
Views: 19 Gene Music Studio
Gene Music using Protein Sequence of ARHGEF37 "RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 37"
 
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Gene Music using Protein Sequence of ARHGEF37 "RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 37" Subscribe ➜ https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1
Gene Music using Protein Sequence of RAPGEF1 "RAP GUANINE NUCLEOTIDE EXCHANGE FACTOR 1"
 
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Gene Music using Protein Sequence of RAPGEF1 "RAP GUANINE NUCLEOTIDE EXCHANGE FACTOR 1" Subscribe ➜ https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1 Gene Music Studio - A channel to taste (visually & musically) gene information (particularly protein sequences).
Gene Music using Protein Sequence of RAPGEF4 "RAP GUANINE NUCLEOTIDE EXCHANGE FACTOR 4"
 
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Gene Music using Protein Sequence of RAPGEF4 "RAP GUANINE NUCLEOTIDE EXCHANGE FACTOR 4" Subscribe ➜ https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1 Gene Music Studio - A channel to taste (visually & musically) gene information (particularly protein sequences).
Gene Music using Protein Sequence of ARHGEF18 "RHO/RAC GUANINE NUCLEOTIDE EXCHANGE FACTOR 18"
 
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Gene Music using Protein Sequence of ARHGEF18 "RHO/RAC GUANINE NUCLEOTIDE EXCHANGE FACTOR 18" Subscribe ➜ https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1 Gene Music Studio - A channel to taste (visually & musically) gene information (particularly protein sequences).
Gene Music using Protein Sequence of RAPGEF6 "RAP GUANINE NUCLEOTIDE EXCHANGE FACTOR 6"
 
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Gene Music using Protein Sequence of RAPGEF6 "RAP GUANINE NUCLEOTIDE EXCHANGE FACTOR 6" Subscribe ➜ https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1 Gene Music Studio - A channel to taste (visually & musically) gene information (particularly protein sequences).
Views: 10 Gene Music Studio