Lecture 6-7,9,11 + Textbook chap 15 Flashcards
cell signaling
The process by which information from the extracellular molecules is translated to an internal cellular signal
Cells usually communicate with one another through
extracellular messenger molecules
Autocrine/paracrine signaling (2)
- the cell that is producing the messenger expresses receptors on its surface that can respond to that messenger. Consequently, cells releasing the message will stimulate (or inhibit) themselves
- messenger molecules travel only short distances through the extracellular space to cells that are in close proximity to the cell generating the message. Paracrine messenger molecules are usually limited in their ability to travel around the body because they are inherently unstable, or they are degraded by enzymes, or they bind to the extracellular matrix.
endocrine signaling (2)
system+ sites
- messenger molecules reach their target cells via passage through the bloodstream
- Endocrine messengers, also called hormones, typically act on target cells located at distant sites in the body
Juxtacrine signaling
Both the ligand and receptor are membrane bound (not secreted) and in close proximity
second messenger
small non-protein molecules that typically activate (or inactivate) specific proteins to amplify the signal inside the cell
Kinase vs phosphatases
kinase adds phosphates while phosphatases removes them
signal transduction
information carried by extracellular messenger molecules is translated into changes that occur inside a cell
Signals transmitted along such signaling pathways ultimately reach —— involved in basic cellular processes. Depending on the type of cell and message, the response initiated by the —— may involve a change in gene expression, an alteration of the activity of metabolic enzymes, a reconfiguration of the cytoskeleton, an increase or decrease in cell mobility, a change in ion permeability, activation of DNA synthesis, or even the death of the cell.
- target proteins
Signal transduction pathway consisting of protein kinases and protein phosphatases
Signal transduction pathway consisting of protein kinases and protein phosphatases with catalytic actions that change the conformations, and thus the activities, of the proteins they modify. In the example depicted here, protein kinase 2 is activated by protein kinase 1. Once activated, protein kinase 2 phosphorylates protein kinase 3, activating that enzyme. Protein kinase 3 then phosphorylates a transcription factor, increasing its affinity for a site on the DNA. Binding of a transcription factor to the DNA affects the transcription of the gene in question. Each of these activation steps in the pathway is reversed by a phosphatase.
Finally, signaling at the end of signaling transduction must be terminated. This is important because cells have to be responsive to additional messages that they may receive. The first order of business is to eliminate the extracellular messenger molecule. To do this……..
Certain cells produce extracellular enzymes that destroy specific extracellular messengers. In other cases, activated receptors are internalized. Once inside the cell, the receptor may be degraded along with its ligand, which can leave the cell with decreased sensitivity to subsequent stimuli.
Control of signal transduction
- cell type specific expression of ligand-specific receptor
- timing of docking protein activation
- prescence/abscence of docking sites
- inhibitory proteins prevent certain signals
Jack STAT pathway (7):
- Prolactin binds to the prolactin receptor (cytokine receptor)
- The two receptor chains dimerize upon prolactin binding
- Jack will get active by autophosphorylation
- Jack also phosphorylate the receptor chains
- When Jack is active, it will activate STAT by phosphorylating STAT
- STAT combine with another STAT (dimerization) with the phosphate group and phosphorylated tyrosine attached to each
- STAT travel to the nucleus to increase transcription
G protein-coupled receptors (GPCRs)
- ## These receptors translate the binding of extracellular signaling molecules into the activation of GTP-binding proteins.
Receptor protein-tyrosine kinases (RTKs)
- Binding of a specific extracellular ligand to an RTK usually results in receptor dimerization followed by activation of the receptor’s protein kinase domain which is present within its cytoplasmic region.
- Upon activation, these protein kinases phosphorylate specific tyrosine residues of cytoplasmic substrate proteins, thereby altering their activity, their localization, or their ability to interact with other proteins within the cell.