Books for lectures / !!! SignMolecDiffProlif Pictures

SH-2 groups on proteins bind phosphotyrosine

SH-3 groups on proteins bind proline-rich regions

G-Protein Coupling

●activation of adenylate cylcase

–eg, glucagon receptor

●activation of PLCγ

–eg, angiotensin, vasopressin, bradykininnin

●activation of phosphodiesterase

–transducin in photoreception

Glucagon and epinephrine as examples of cAMP-mediated signaling

G-Protein Regulators

●GAPs: GTPase activating proteins

–eg, rasGAP

–NF1 (neurofibromin) a tumor suppressorsor

–BCR locus in CMLs and ALLs

G Protein cycle of activation and inactivation

G Proteins contain intrinsic GTPase activity

Accessory Factors

GEF

Guanine nucleotide Exchange Factor

GAP

GTPase Activating Protein

GDI

Guanine nucleotide Dissociation Inhibitor

Activation of Ras signaling pathway by an RTK

Phosphotyrosine on receptor is bound by adaptor protein, which binds and activates Guanine Nucleotide Releasing Protein (GNRP) (also GEF). GNRP activates Ras; Ras activates a kinase cascade. Ras GTPase is activated by GAP, turning the pathway off.

Ras activation of MAP Kinase

Once Ras is activated, it activates a series of kinases, beginning with the Raf kinase (MAPKKK)

Raf activates MAPKK (MEK)

MAPKK activates MAPK (ERK)

MAPK activates transcription factors