Chapter 8 Flashcards
Fill in either the Growth Factor Receptor or the ligand that binds it
LIGAND GFR
kit
Met
Her2
LIGAND GFR
Kit SCF Receptor
Hepatocyte GF Met
ECFR (speficically Epiregulin) Her2
What are the 3 main structural components of the receptor protein tyrosine kinases?
What is the function of each structural component?
Extracellular domain:
main distinguishing feature of the RTK subgroups is in this part as the amino terminus determines the binding domain
Hydrophobic helix:
single short transmembrane component connects the other two segments
Intracellular (cytoplasmic domain):
Has a kinase domain which catalyzes the transfer of a phosphate group from ATP onto a protein substrate (usually a tyrosine - hence the name RPTK)
Binding of a growth factor on the extracellular domain causes how many growth factor receptors to join together?
2 = dimerization
This joining together is nb because it leads to conformational switches in the cytoplasmic domain that are required for full catalytic activity
Once activated, receptor protein tyrosine kinases activate intracellular signaling by binding w/ specific proteins. This is accomplished by the use of noncatalytic domains that bind specifically to short regions of the target protein. Proteins most often recognized by RPTKs often contain either (what 2 sequences)
SH2 - Src homology 2 -or-
PTB - phosphotyrosine binding domains
Ras proteins are membrane associated molecules that actively signal when bound to ___. Ras is activated by SOS (son of sevenless) - a guanine nucleotide exchange protein that releases bound ____ so that a new ____ can be bound. The action of these proteins is countered (negatively regulated by) the action of GAPs (which are _____). Ras is important in regulating normal cell growth. There are 3 distinct Ras protein isoforms (they are ___, ___, and ___). Each has a molecular weight of _____ making the designation for this protein p21 Ras. When RAS function is active it results in activation of ____ (name 3 downstream molecules) and results in cell cycle progression, transcription and survival.
Finally, Ras proteins need post-translational modifications for normal function. They are processed by a ____ that adds a farnesyl group to allow association with intracellular membranes which localizes the proteins to particular parts of the membrane as needed for normal function.
GTP GDP GTP GTPase activating proteins H, K, and N 21 kilodaltons Raf-1 to activate Mek and then ERK farnesyl transferase
Phosphoinositidines are phospholipids from ___. They are dynamically regulated in response to GF signaling. They contribute to signal propagation via two main mechanisms. The first is by serving as precursors of the second messengers __ and ___ and the second is by binding to signaling proteins that have PI binding.
cell membranes
DAG
IP3
PTEN (negatively/positively) affects P13K
negatively
Transciption factors can be divided into 4 groups based on the structure of their DNA binding domain. Name the 4 groups and examples of each.
Homeodomain (or helix turn helix); Oct 1
Zinc Finger; glucocorticoid receptor
Leucine zipper; c-jun, fos/jun, AP-1
Helix-loop-helix; myc
Nora cells in G1 phase must either exit the cell cycle into ___ or pass through the ___ (checkpoint) which commits the cell to undergoing cell cycle division
G0
Restriction point
Cyclin/CDK complexes are key proteins in regulating cell cycle progression. Which cyclin is primarily responsible for regulating Rb protein? How does it do this?
Cyclin D with its corresponding CDK phosphorylates and inactivates the RB protein which results in release of E2F which is required for the cell to enter S phase
Downregulation of receptors on the cell surface is one way cells regulate activity. Receptors are removed by endocytosis (internalization) and degradation.
Explain the degradation process.
Be sure to mention which enzyme controls which proteins are degraded.
Ubiquitin is first attached to E1 (a ubiquitin activating enzyme) and is then transferred to a ubiquitin-conjugating enzyme (E2). E2 works with E3 (ubiquitin ligase) to transfer UB to a specific protein (in this case the receptor).
E3 ligase is responsible for the specificity of this process by selectively binding substrates.
Cytokine receptors do not contain intrinsic tyrosine kinase activity (like the RPTKs).
Instead they transmit intracellular signaling through their association w/ what family of tyrosine kinases?
JAK - janus kinases
Most cytokine receptors have a unique extracellular ligand binding region, a single transmembrane domain and a cytoplasmic domain. Most of the receptors exist as single or multisubunit chains?
MULTI - except EPO and GCSF
What is the function of the STAT proteins?
What protein activates them?
STAT proteins are signal transducers and activators of transcription.
They are phosphorylated, are transported into the nucleus, where they regulate gene transcription.
JAK activates
TCR (T cell receptor) is a heterodimer composed of Alpha and Beta subunits.
With a ligand binding domain at the amino terminus and constant region, the TCR is associated w/ what complex?
CD3
