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Enzyme-coupled receptors
enzymatic activity or are associated with enzymes. (Most of them are kinases or associate with kinases)
function of Enzyme-linked receptors
- often involved in cell growth & movement
- ligands typically = growth factors
some attached to cell surface
- cytosolic receptor domain = enzyme or directly associates with enzyme
- genetic defects can lead to uncontrolled cell proliferation
6 classes of enzyme-linked receptors
•Tyrosine kinases
•Tyrosine kinase-associated
•Tyrosine phosphatases
•Serine/threonine kinases
•Histidine-associate kinase
•Guanylyl cyclase
Receptor Tyrosine Kinases (RTKs)
secreted peptide growth factors and peptide hormones
- extracellular ligand-binding domain
- single transmembrane domain
- intracellular tyrosine kinase domain
- activation of the receptor induces a conformational change, which causes receptors to dimerize
- two kinase domains brought together by dimerization activate each other
- phosphorylation activates kinase activity of RTK
where are other ligands bound to?
cell surface upon which the target cell crawls
Ephrin receptor - ephrin interaction is involved in ________-_________ signaling
contact-dependent
Eph receptors are (1)____
- largest class of membrane-bound ligands
- help guide migration of ___ & _____; important in development
(1) RTKs
(2) cells & axons
Ephrin receptor
Act both ways: activated Eph receptors are transmitting signal back to signaling cell
- behavior of both signaling cell and target cell are altered
*bidirectional signaling is important..?
to prevent cells of different tissues from mixing
Which of the following usually goes both ways (signaling cell-target cell and target cell-signaling cell)?
•A. Any receptor tyrosine kinase signaling
•B. Signaling through Ephrins
•C. Signaling through GPCRs
•D. All of the above
•B. Signaling through Ephrins
Cross-phosphorylation stimulates kinase activity & creates high affinity _________ ______ for other proteins
docking sites
_________ _______ prevent cross-talk between parallel MAP kinase molecules
scaffold proteins
role of scaffold proteins
organize multiple signaling proteins into larger complexes; enhancing SPEED, EFFICIENCY, AND SPECIFICITY; bring the kinases into close proximity
Sometimes an _______ (_________) __________ can function as a scaffold protein
activated (phosphorylated) receptor
A single extracellular signal can initiate multiple distinct signal transduction cascades, leading to _________ ________.
multiple outcomes (i.e, change in cell shape, and cell movement)
Proteins with _____ or ______ interaction domains bind to phosphorylated tyrosines at RTKs
SHR or PTB
which protein domain is the most common?
SH2
- can recognize phosphorylated tyrosines
- can be inserted anywhere in the protein without disturbing its structure and function
- link RTKs to different signaling pathways
the assembly of signaling complexes depends on __________ __________
- they are compact
- bind to certain structural motifs
interaction domains
interaction domains of signaling proteins are _________ ___________
highly conserved