Molecular Biology

Autocrine

a chemical signal that binds to and affects the cell that makes it

Paracrine

Referring to a secreted molecule that acts on a neighboring cell.

Endocrine

Signaling pathway that passes through the blood and acts on a distant cell or tissue.

Juxtacrine

signals act through direct stimulation of the adjacent cells

Stanley Cohan

1940s and 50s. Took salivary gland extract and injected it into newborn mice and caused premature eye opening. Isolated EGF that did this.

Sis

Simian Sarcoma Virus, PDGF protein, found in SERA

SERA

Clotting factor and plasma mixture

PDGF

platelet derived growth factor

Fibroblast Growth Factor (FGF)

A peptide growth factor, originally defined by its mitogenic effects on fibroblasts.

receptor tyrosine kinases

Group of proteins to signal cell proliferation
Has:
Ligand binding
Transmembrane domain
Tyrosine Kinase domain
c-terminal domain

V-erbB

Viral version of EFG, missing ligand binding domain

HER2/neu (ErbB2)

can't bind to ligands, always in ligand bound conformation. Generally used in heterodimer (limited binding with self)

ERBB3
(Her3)

Missing tyrosine kinase domain. Requires help for transphosphorylation

v-Src

Has oncogene attached in viral version. Is a tyrosine-protein kinase

RSV

Transformation of this retrovirus leads to increase of p-tyrosine but not p-ser or p-thr

Tony Hunter

Found phosphotyrosines because he didn't remake buffer.

Myristoylation

attachment of lipid chains resulting in membrane localization of a protein

SH3 Domain

binds proline rich sequences

SH2 Domain

A protein domain that binds phosphorylated tyrosine residues.

SH1 Domain

tyrosine kinase domain - phosphorylates Y

C terminus

end of src protein that has Tyr in it that can be phosphorylated

Inactive src

Proline-rich sequence attached to self. SH2 domain attached to C-terminal domain

Active src

Proline rich sequence opened, C-terminus phosphorylated and out of SH2 domain or missing

Ras

GTPase, bind and hydrolyze the gamma phosphate in GTP. Most popular of family

Sos (son of sevenless)

GEF (guanine exchange factor) in Ras. Lets Ras let go of GDP.

GAP

GTPase activating protein - is a tumor suppressor

Grb2 and Shc

Linker proteins from Ras to RTK

Protein Prenylation

C-terminal lipid modification of some membrane proteins at cysteines

Protein Palmitoylation

attachment of palmate group via thioester or amide linkage

Myc

Unstable protein that causes cell proliferation using a ton of ways

Integrin Signaling pathway

Uses FAK (Focal Adhesion Kinase) then Src. Otherwise same as EGF receptor signal transduction pathway.

FAK

Focal adhesion kinase

Notch Receptor

Acts as a transcription factor; contact dependent cell to cell signaling; inhibits neuronal differentiation. Breaks off and goes into cell

unilateral retinoblastoma

Caused by somatic Rb mutation

bilateral retinoblastoma

Caused by inherited mutation

Gene Conversion

the process by which one DNA sequence replaces a homologous sequence such that the sequences become identical after the conversion event

mitotic recombination

crossing over that occurs during mitosis and produces a pair of recombinant chromosomes

Loss of heterozygosity (LOH)

when a heterozygous somatic cell incurs a genetic change that inactivates the single functional allele

mitotic nondisjunction

an event in which chromosomes do not segregate equally during mitosis

Chromosomal Deletion

A mutation involving the loss of a section of a chromosome

Promoter Methylation

Methylation of promoter gene of tumor suppressor. Can cause same phenotype as LOH

NF-1

Mutation in this gene causes Fibromas. Found by Ray White and Francis Collins

Adenomatous polyposis coli (APC)

tumor suppressor gene. --> sporadic colon cancer and familial adenomatous polyposis

beta-catenin

active TF(transcription factor) when complexed with member of TCF or LEF family ? synthesis of surviving & mitotic proteins

Wnt

Primary messenger signals to turn off APC

Wnt Pathway

what is an important signaling pathway that regulates the cell cycle machinery to control cell proliferation and uses the GSK3B enzyme

Frizzled

receptor of Wnt in the Wnt pathway