Cell signaling

Type	Response to	Receptor	Enzyme
Membrane-penetrating receptors possessing intrinsic enzymatic activity.	EGF, FGF, insulin, PDGF receptors	Receptor tyrosine kinases (RTKs) capable of autophosphorylation as well as phosphorylation of other substrates. Tyrosine phosphatases. Guanylate cyclases (natriuretic peptide receptors). Serine/threonine kinases, TGF-beta receptors	Receptor tyrosine kinases (RTKs), Tyrosine phosphatases, (CD45). Guanylate cyclases. Serine/threonine kinases.
Membrane-penetrating receptors connected to intrinsic enzymatic activity.	Activins, inhibins, bone morphogenetic proteins (BMPs), TGF-beta receptors	Receptors (RTKs) coupled to intracellular protein tyrosine kinases by direct protein-protein interactions	Protein tyrosine kinases
GPCRs	hormones: adrenaline, glucagon, luteinizing hormone (LH), parathyroid hormone (PTH), adrenocorticotropic hormone (ACTH)*, rhodopsin**, growth factors***	GPCRs, or guanine nucleotide-binding protein-coupled receptors, or serpentine receptors. ***Receptors coupled to activation of phospholipase C-gamma	G-proteins → second-messenger → activated enzymes: *adenylyl (adenylate) cyclase → second-messenger cAMP → cAMP-dependent protein kinase, (PKA) **guanyl cyclase → second messenger cGMP → protein kinase G (PKG) ***DAG & IP3 -protein kinase C (calcium dependent)
Intracellular receptors that migrate to the nucleus after binding to the ligand – to directly affect gene transcription	Lipophilic steroid and thyroid hormones, incl. glucocorticoid, vitamin D, retinoic acid, and thyroid hormones.	Hormone receptors are cytoplasmic proteins that bypass membrane-bound signal transduction pathways.	Hormone-receptor complex translocates to the nucleus and binds to specific DNA sequences (hormone response elements, HREs).
two-component systems	Nutrient acquisition : nitrogen, phosphorus, carbon. Chemotaxis. Energy metabolism : electron transport systems, uptake and catabolic machinery. Developmental pathways. Virulence : plasmid transfer (conjugation), degredative secretions, toxin production	Transmitter domain - histidine kinase protein autophosphorylates a histidine, then transfers the phosphoryl group to an aspartate residue of the partner response regulator protein	Receiver domain - response regulator protein is activated by phosphorylation and then transmits the signal to its target

 Cell signaling  Receptor Tyrosine Kinases(RTK)  Second Messengers  Phosphate-handling Enzymes  · adenylyl (adenylate) cyclase · calcium ion · calcium ions · cAMP-dependent protein kinase · CDKs · cyclin-dependent kinases · DAG · diacylglycerol · DNA ligases · ERKs· GPCRs · GPCR families · guanylate cyclases · guanyl cyclase · inositol triphosphate · IP3 · MAP kinases · mitogen activated protein kinases · phosphatases · phosphodiesterases · phospolipases · phosphorylation · PKA · PKC · phospholipase C-gamma · protein kinase A · protein kinase C · protein tyrosine kinases (PTKs) · receptor tyrosine kinases · second messengers · second messenger cAMP · second messenger cGMP · signal transduction · two-component systems ·

Receptor Tyrosine Kinases (RTKs)

Class	Examples	Structural Features of Class
I	EGF receptor, NEU/HER2,HER3	cysteine-rich sequences
II	insulin receptor, IGF-1 receptor	cysteine-rich sequences; characterized by disulfide-linked heterotetramers
III	PDGF receptors, c-Kit	Contain 5 immunoglobulin-like domains; contain the kinase insert
IV	FGF receptors	Contain 3 immunoglobulin-like domains as well as the kinase insert; acidic domain
V	vascular endothelial cell growth factor (VEGF) receptor	Contain 7 immunoglobulin-like domains as well as the kinase insert domain
VI	hepatocyte growth factor (HGF) and scatter factor (SC) receptors	Heterodimeric like the class II receptors except that one of the two protein subunits is completely extracellular. The HGF receptor is a proto-oncogene that was originally identified as the Met oncogene
VII	neurotrophin receptor family (trkA, trkB, trkC) and NGF receptor	Contain no or few cysteine-rich domains; NGFR has leucine rich domain