BIOL 688 Exam 2 Terms to Know

Signal transduction

Process of transferring signals from extracellular environment to intracellular organelles

Receptor

Protein that binds a signal molecule and initiates a cellular response

Autocrine

Signal released by a cell and acts upon the same cell that released it

Paracrine

Signal that acts on nearby cells

Endocrine

Signal that acts on cells in another tissue at a distant site, usually through the bloodstream

Juxtacrine

Intercellular communication through physical contact

Mitogen

Extracellular substance that stimulates mitosis

Growth factor

Substance that stimulates growth and/or proliferation

EGF

Epidermal growth factor

Stanley Cohen

Scientist who discovered EGF and its role in epidermal growth

Rita Levi-Montalcini

Scientist who discovered NGF (Nerve Growth Factor)

TGF-a

Transforming Growth Factor alpha, binds to the same receptor as EGF

PDGF

Platelet Derived Growth Factor, stimulates cell proliferation and is contained in platelets

Sis

Oncogene from Simian Sarcoma Virus, transforms fibroblasts and increases PDGF expression

Plasma

Liquid left after removing cells from blood without clotting

Serum

Liquid remaining after blood clotting and removal of cells

Platelets

Blood cells involved in clotting

FGF

Fibroblast Growth Factor, stimulates fibroblast proliferation

Transmembrane domain

Protein domain that spans the cell membrane

Tyrosine kinase

Enzyme that attaches phosphate groups to proteins using ATP

Nusse and Varmus

Scientists who identified c-src and insertion points of cancers

MMTV

Mouse Mammary Tumor Virus, used to identify FGF3 as an insertion point of cancer

Dimerization

Process of two identical proteins coming together to form a functional assembly

Heterodimer

Protein composed of two different polypeptide chains

Homodimer

Protein composed of two identical polypeptide chains

Receptor tyrosine kinase (RTK)

Subclass of tyrosine kinases involved in cell-to-cell communication

EGFR/ErbB1/HER1

Epithelial Growth Factor Receptor, responds to TGF-alpha and EPR growth factors

v-ErbB (vs. c-EGF-R)

v-____is a viral oncogene that makes EGF-R constitutively active, c-___-_ has an extra ligand binding ectodomain

ErbB2/HER2/Neu

Gene family always in active conformation, discovered in rat neuroblastoma

ErbB3/HER3

Gene family that lacks Tyr Kinase Domain and responds to NRG1 and NRG2

ErbB4/HER4

Gene family that responds to NRG1-4 and EPR

Transphosphorylation

Transfer of a phosphate group from one kinase to another

Tony Hunter

Scientist who showed that Tyr can be phosphorylated

Non-receptor tyrosine kinase

Sub-group of tyrosine kinases that relay intracellular signals

SRC

Non-receptor tyrosine kinase

ABL

Gene that can stimulate cell proliferation or differentiation

SH1

Component of Src that adds phosphate to another protein

SH2

Component of Src that binds phospho-Tyr

SH3

Component of Src that binds proline rich regions

SH4

Component of Src that is membrane localized and does myristoylation

Myristoylation

Adding lipid to protein and attaching it to the plasma membrane

Integrin

Protein that interacts with extracellular matrix proteins

Attachment-dependent proliferation

Cells proliferate as long as they are attached to a surface and have a source of nutrition

v-Abl (vs. c-Abl)

v-___ has a fusion of tyrosine kinase with Gag, c-___ has a SH3 domain and no Gag

BCR-ABL

Fusion gene resulting from translocation of genes from chromosome 9 and chromosome 22

Gleevec

Drug that protects against ABL-tyrosine kinase

Chronic Myelogenous Leukemia (CML)

Cancer of the bone marrow caused by the BCR-ABL fusion gene

RAS

GTP-binding protein that causes Rat Sarcomas

GTPase

Protein that binds and hydrolyzes GTP

GEF (guanine nucleotide exchange factor)

Protein that removes GDP to allow GTP to enter

GAP (GTPase activating protein)

Protein that does GTP hydrolysis and RAS inactivation

Son of sevenless (SOS)

Protein that removes GDP so Ras can be activated

Grb2

Adaptive protein that contains SH2 and SH3 domains

Shc

Adaptive protein that binds to Grb2

RAF/MAPKKK

Protein attracted after EGF binding in signaling pathway

MEK/MAPKK

Protein attracted after EGF binding in signaling pathway

ERK/MAPK

Protein attracted after EGF binding in signaling pathway

MYC

Transcription factor that can result in Burkitt's lymphoma and other malignancies

Tyrosine vs. Serine/Threonine phosphorylation

Serine/Threonine phosphorylation is more stable than tyrosine phosphorylation

FAK (Focal adhesion kinase)

Tyrosine kinase present in the integrin binding pathway

Notch

Receptor involved in cell proliferation and development

Delta

Ligand that activates the Notch signaling pathway

TGF-b

Ligand that can stop the growth of many cell types

TGF-b type II vs. type I receptor

Type II receptor binds the TGF-beta ligand and keeps an already active ser/thr kinase before the ligand binds

Smad

Proteins that inhibit cell growth when activated by TGF-b signaling

PP2A

Protein phosphatase 2A, implicated in cell growth and signaling

Tumor suppressor

Counterbalance for oncogene, regulates cell growth and prevents tumor formation

Retinoblastoma/ RB

Tumor suppressor gene that controls cell cycle entry

Bilateral

Retinoblastoma occurs in both eyes or multiple times in one eye

Unilateral

Retinoblastoma occurs in one eye and diagnosed at a later age

Alfred Knudson

Scientist who developed the 'two hit' model for retinoblastoma

'Two hit model' for inactivation of a tumor suppressor

If both alleles of a tumor suppressor gene become mutated, tumor formation can occur

Ray White/Web Cavenee

Researchers who showed loss of function of Rb resulted in retinoblastoma

Loss of heterozygosity (LOH)

Loss of one parent's contribution to the cell

Gene conversion

Process of DNA polymerase copying a segment from one homologous chromosome to another

Mitotic recombination

Recombination of homologous chromosomes during G2 or M phase

Mitotic nondisjunction

Inappropriate chromosome separation during mitosis

Pedigree

Family tree listing affected and non-affected individuals for a particular trait/disease

Neurofibromatosis (NF)

Benign peripheral nerve sheath tumors caused by mutations in the NF1 gene

Francis Collins

Researcher who discovered NF-1

Ray White

Researcher who worked with Francis Collins to discover NF-1

APC

Gene and protein product that can result in colon polyps if mutated

Wingless/Int-1 = Wnt

Gene involved in wing development in flies, mutated version called Wingless

White/Vogelstein/Nakamura

Researchers who identified the APC gene

b-catenin

Protein that binds to APC and is targeted for destruction

Christiane Nusslein-Volhard and Eric Wieschaus

Researchers who discovered the Wg gene in flies

Roel Nusse and Harold Varmus

Researchers who discovered Wnt and identified cellular-src

Ubiquitination

Posttranslational modification that marks proteins for degradation

Ubiquitin ligase (E1, E2, E3)

Ligase complex that attaches ubiquitin to proteins

Proteasome

Enzyme that breaks down targeted proteins into peptides

Axin

Protein that binds to APC and attracts beta-catenin

Gsk-3b

Protein that is attracted to Axin and APC binding, resulting in beta-catenin attraction

Frizzled (Fz)

Gene receptor for Wnt

Dishevelled

Gene that is activated or deactivated by Frizzled depending on Wnt signal

LEF-1

Transcription factor for cell proliferation

MYC/MAX

Activating promoters of proliferation

MYC/MIZ

Blocking inhibitors of proliferation

Cell cycle phases

G0, G1, S, G2, M

Cell cycle checkpoints

G1, S, G2, M checkpoints that regulate cell cycle progression

Tim Hunt

Scientist who discovered cyclin