Cell Bio 102 Cell Signaling Pathways

1) Transform initial signal into form suitable for passing signal 2) relay signal from receptor point to produce a response 3) amplify signal 4) distribution of signal to influence several processes at once 5) modulation of signal by factors inside and outside of cell

What are the five parts of a signaling cascade?

Relaying signal from receptor point. Regulate signal transduction and localize pathway components.

What step of a signaling cascade are scaffolding proteins involved in? What is the purpose of scaffolds?

Membrane anchored proteins that bind too large or hydrophilic ligands that cannot cross the membrane. Contain extracellular binding domain, hydrophobic domain extending through membrane, intracellular domain that transmits the signal

What are cell surface receptors? What are the three parts?

Cause neighboring RTKs to associate with each other, forming cross-linked dimers

When signaling molecules bind to RTKs, what does the RTK do and what does this form?

phosphorylation of a kinase by the other identical kinase in the dimer

What is transautophosphorylation?

GRB 2 scaffolding protein

To relay a signal after transautophosphorylation of RTKs, what is recruited?

Ras bound to GDP recruits guanosine exchange factors (GEF)

The docking of GRB 2 scaffolding proteins in RTK signaling recruits what enzyme? To convert GDP to GTP, what is recruited?

MAP KKK (Raf) phosphorylates MAP KK (MEK). MAP KK phosphorylates MAP K (ERK)

After Ras binds to GEFs in RTK signaling, what is the MAP K cascade?

Transcription factors recruit DNA replication machinery such as DNA polymerase III, helicase, SSB proteins, and ligase

After the MAP K cascade in RTK signaling, what is recruited? What will these factors recruit in DNA replication?

GAP and GTPase activating proteins

To stop signaling, although phosphatase will hydrolyze MAP K pathway to remove phosphate, what will deactivate RAS?

heterotrimeric G protein where alpha subunit is bound to GDP

What is the ligamerization of a GPCR without a ligand?

alpha and gamma, lipids

What two out of the three subunits in a GPCR are integrated into the membrane? How?

Secondary messengers to amplify the enzyme that have intristic GTPase activity to turn off the signal

After alpha subunit binds to GTP and dissociates from the trimeric complex, what will it recruit? What is the purpose of these messengers?

adenylyl cyclase and phospholipase C

What are the two possible secondary messengers in GPCR coupling?

cyclic AMP

ATP becomes what in adenylyl cyclase secondary messenger?

diacylglycerol (DAG) and inositol triphosphate (IF3)

Phospholipase C becomes what two components?

PKA (AMP dependent protein kinase) consists of a regulatory subunit, cAMP binding site, and catalytic subunit. cAMP binds causing the regulatory subunit to dissociate and activate the catalytic site.

What does cAMP activate? What are the components of this enzyme?

Transcription factors in the nucleus like CREB

What does PKA activate? Provide an example

cAMP phosphodiesterase breaks cyclic to become AMP at the regulatory subunit, phosphatase hydrolyzes phosphate on transcription factor, GAP (RGS) binds directly to enzyme

Describe three levels of regulation in adenylyl cyclase GPCR

Calcium channel in the ER binds to PKC and cleaved phospholipid part

Polar IP3 released in the cytosol in GPCR coupling will open up what channel? What will it bind to?

Membrane, PKC

DAG, after phospholipase C activation, will stay where and bind to what?

GRK (like RGS) and arrestin (acts like adaptins)

What two regulatory proteins are involved in turning off the GPCR cascade?