Cell Signaling Flashcards
Specificity of receptor-ligand interactions is governed by _____ structure and _______ bonds between _____.
Specificity of receptor-ligand interactions is governed by TERTIARY structure and NON-COVALENT bonds between AMINO ACIDS.
Ion channels are important for: Transport of \_\_\_\_ and \_\_\_\_\_ Chemical signaling (\_\_\_ channels) Regulation of cellular \_\_\_\_\_ and \_\_\_\_\_ \_\_\_\_\_ of intracellular organelles
Ion channels are important for: Transport of SALT and WATER Chemical signaling (Ca2+ channels) Regulation of cellular VOLUME and pH ACIDIFICATION of intracellular organelles
The ligand for CFTR is ____
Mutation in CFTR results in abnormal ____ transport across _____ cell membranes, resulting in ________ in respiratory _____ cells.
The ligand for CFTR is ATP
Mutation in CFTR results in abnormal SALT transport across EPITHELIAL cell membranes, resulting in THICK MUCUS BUILD-UP in respiratory EPITHELIAL cells.
Gain of function mutations in ion channels are typically associated with _____ inheritance of the disease. Usually results in ______ activation.
Mutations in Na+ channels can result in _______ and _______ in _____, _____ and ____.
Gain of function mutations in ion channels are typically associated with DOMINANT inheritance of the disease. Usually results in CONSTITUTIVE activation.
Mutations in Na+ channels can result in DEFECTIVE INACTIVATION and LATE Na+ CURRENTS in PARAMYOTONIA, CARDIAC ARRHYTHMIA and EPILEPSY.
Tetrodotoxin is a _____ channel blocker
Tetrodotoxin is a SODIUM channel blocker
Nuclear steroid hormone receptor mech of action:
Receptor is usually found in _____. When ligand is not bound, receptor usually binds to ______. The ligand can displace the ______, exposing an ___ so the lignad-receptor complex can enter and act as transcription factors by binding to ____. These receptors _____ either before or entering nucleus, and this is necessary for acticvation (if _________ is a part of the specific pathway)
Receptor is usually found in CYTOPLASM (CAN ALSO BE FOUND IN NUCLEUS). When ligand is not bound, receptor usually binds to CHAPERONE. The ligand can displace the CHAPERONE, exposing an NLS so the lignad-receptor complex can enter and act as transcription factors by binding to HREs. These receptors DIMERIZE either before or entering nucleus, and this is necessary for acticvation (if DIMERIZATION is a part of the specific pathway)
This example was specific for estrogen
Treatment of estrogen-sensitive breast cancer:
ER+ breast cancer cells require _____ for cell division and DNA replication.
Endocrine therapy involves the use of ER ______ such as _____.
In breast tissue, _____ is metabolized into a protein, ________ that binds to the E-receptor and prevents __________.
ER/_____ complex functions to _______ estrogen target genes via _____________.
Treatment of estrogen-sensitive breast cancer:
ER+ breast cancer cells require SIGNALING for cell division and DNA replication.
Endocrine therapy involves the use of ER ANTAGONISTS such as TAMOXIFEN.
In breast tissue, TAMOXIFEN is metabolized into a protein, H-TAM that binds to the E-receptor and prevents BINDING OF ESTROGEN.
ER/H-TAM complex functions to REPRESS estrogen target genes via RECRUITMENT OF TRANSCRIPTIONAL CO-REPRESSORS.
Protein kinase receptors either have a ______domain or _______________.
They are made up of: _____ domain that binds ligand, ______ domain, and the domain mentioned above.
Active receptors contain typically _ or more polypeptide chains (they must _____ for activation).
Ligand binding induces ______ which leads to ____. Cascade of _____ occurs after ______.
Two major subfamilies:
_____ kinases —> insulin, EFG, FGF, PDGF, VEGF, Trk
_____ kinases —> cytokines, TGF-B
Protein kinase receptors either have a INTRACELLULAR PK domain or BINDS A PK PROTEIN.
They are made up of: EXTRACELLULAR domain that binds ligand, TRANS-MEMBRANE domain, and the domain mentioned above.
Active receptors contain typically TWO or more polypeptide chains (they must DIMERIZE for activation).
Ligand binding induces CONFORMATIONAL CHANGE which leads to DIMERIZATION. Cascade of PHOSPHORYLATION occurs after DIMERIZATION.
Two major subfamilies:
TYROSINE kinases —> insulin, EFG, FGF, PDGF, VEGF, Trk
SERINE/THREONINE kinases —> cytokines, TGF-B
Mechanism of PK Receptor Activation
Ligand binds extracellular domain of ____ receptor subunit.
Subunits _____, binding _____ _____ domains closer together.
_____ ______ and activate each other.
Activated ____ are often ______ at multiple positions.
Additional ______ proteins bind ______ receptors (via _____).
Mechanism of PK Receptor Activation
Ligand binds extracellular domain of EACH receptor subunit.
Subunits DIMERIZE, bringing CYTOSOLIC PK domains closer together.
KINASES PHOSPHORYLATE and activate each other.
Activated KINASES are often PHOSPHORYLATED at multiple positions.
Additional CYTOSOLIC proteins bind PHOSPHORYLATED receptors (via RECRUITMENT).
Grb protein ________ due to ________ in RTKs. It binds ______ via it’s ____ domain which recognizes ____.
Grb protein RECOGNIZES CONFORMATIONAL CHANGE due to PHOSPHORYLATION in RTKs. It binds PHOSPHORYLATED RECEPTORS via it’s SH2 domain which recognizes TYR-P.
SoS protein is a _____ protein involved in the ____ pathway, and it binds to ______ in order to activate ________ such as ____.
SoS protein is a GEF protein involved in the RAS pathway, and it binds to GRB in order to activate SMALL G-PROTEINS such as RAS.
GEFS _____ g-proteins by catalyzing _____ of GDP for GTP.
GAPS promote _____ of g-proteins by _______ ______ of GTP to GDP via ________.
G-proteins bind ____ _____ and act as a molecular switch during signaling. They have intrinsic _____ activity.
GEFS ACTIVATE g-proteins by catalyzing EXCHANGE of GDP for GTP.
GAPS promote INACTIVATION of g-proteins by STIMULATING CONVERSION of GTP to GDP via HYDROLYSIS.
G-proteins bind GUANINE NUCLEOTIDES and act as a molecular switch during signaling. They have intrinsic GTPase activity.
Small G-proteins that regulate many aspects of cell function:
Ras: _____ signaling and ____ _______
Rab: _____________
Ran: __________
Rac: ____ cytoskeleton
Small G-proteins that regulate many aspects of cell function:
Ras: RECEPTOR signaling and CELL DIVISION
Rab: TRAFFIC OF MEMBRANE VESICLES
Ran: NUCLEUS/CYTOPLASM TRAFFIC
Rac: ACTIN cytoskeleton
Ras-MAPK Pathway after binding receptor complex:
MAPK ______ activates _____ ______, which stimulate production of proteins involved in _____ ______.
Ras-MAPK Pathway after binding receptor complex:
MAPK CASCADE activates TRANSCRIPTION FACTORS, which stimulate production of proteins involved in CELL DIVISION.
Ras is activated by multiple \_\_\_\_\_\_\_\_\_\_\_. Downstream effectors of ras: \_\_\_\_\_\_\_\_\_ and \_\_\_\_\_\_\_\_ \_\_\_\_\_\_\_\_\_\_ \_\_\_\_ \_\_\_\_\_\_\_\_\_\_ \_\_\_\_\_\_\_ \_\_\_\_\_\_\_\_ \_\_\_\_\_\_\_\_\_
Oncogenic mutations in ras turn all of it’s downstream pathways ___.
Most oncogenic mutations are AA substitution at ______ or _____, which affect the _______ of ras and __________ it’s ability to ________, so it’s always in ______ state.
Ras is activated by multiple LIGAND/RECEPTOR TYPES. Downstream effectors of ras: CELL GROWTH AND DIVISION CYTOSKELETON CELL ADHESION MEMBRANE TRAFFIC ANTI-APOPTOSIS
Oncogenic mutations in ras turn all of it’s downstream pathways ON.
Most oncogenic mutations are AA substitution at GLY-12/13 or GLN-61, which affect the STRUCTURE of ras and ABOLISH it’s ability to HYDROLYZE GTP–>GDP, so it’s always in ACTIVE state.
