Editing Signal transduction (section)

====Tyrosine, Ser/Thr and Histidine-specific protein kinases====
[[Receptor tyrosine kinase]]s (RTKs) are transmembrane proteins with an intracellular [[kinase]] domain and an extracellular domain that binds [[ligand]]s; examples include [[growth factor]] receptors such as the [[insulin|insulin receptor]].<ref name="LiHris">{{Cite journal |vauthors=Li E, Hristova K |date=May 2006 |title=Role of receptor tyrosine kinase transmembrane domains in cell signaling and human pathologies |journal=Biochemistry |volume=45 |issue=20 |pages=6241–51 |doi=10.1021/bi060609y |pmc=4301406 |pmid=16700535}}</ref> To perform signal transduction, RTKs need to form [[protein dimer|dimer]]s in the [[plasma membrane]];<ref name="Schlessinger1988">{{Cite journal |vauthors=Schlessinger J |date=November 1988 |title=Signal transduction by allosteric receptor oligomerization |journal=Trends in Biochemical Sciences |volume=13 |issue=11 |pages=443–7 |doi=10.1016/0968-0004(88)90219-8 |pmid=3075366}}</ref> the dimer is stabilized by ligands binding to the receptor. The interaction between the cytoplasmic domains stimulates the auto[[phosphorylation]] of [[tyrosine]] residues within the intracellular kinase domains of the RTKs, causing conformational changes. Subsequent to this, the receptors' kinase domains are activated, initiating [[phosphorylation]] signaling cascades of downstream cytoplasmic molecules that facilitate various cellular processes such as [[cell differentiation]] and [[metabolism]].<ref name=LiHris/> Many Ser/Thr and dual-specificity [[protein kinases]] are important for signal transduction, either acting downstream of [receptor tyrosine kinases], or as membrane-embedded or cell-soluble versions in their own right. The process of signal transduction involves around 560 known [[protein kinases]] and [[pseudokinases]], encoded by the human [[kinome]]<ref name="pmid12471243">{{Cite journal |vauthors=Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S |date=December 2002 |title=The protein kinase complement of the human genome |journal=Science |volume=298 |issue=5600 |pages=1912–34 |bibcode=2002Sci...298.1912M |doi=10.1126/science.1075762 |pmid=12471243 |s2cid=26554314}}</ref><ref name="pmid24818526">{{Cite journal |vauthors=Reiterer V, Eyers PA, Farhan H |date=September 2014 |title=Day of the dead: pseudokinases and pseudophosphatases in physiology and disease |journal=Trends in Cell Biology |volume=24 |issue=9 |pages=489–505 |doi=10.1016/j.tcb.2014.03.008 |pmid=24818526}}</ref>

As is the case with GPCRs, proteins that bind GTP play a major role in signal transduction from the activated RTK into the cell. In this case, the G proteins are members of the [[Ras superfamily|Ras]], [[Rho family of GTPases|Rho]], and Raf families, referred to collectively as [[small G protein]]s. They act as molecular switches usually tethered to membranes by [[isoprenyl]] groups linked to their carboxyl ends. Upon activation, they assign proteins to specific membrane subdomains where they participate in signaling. Activated RTKs in turn activate small G proteins that activate [[guanine nucleotide exchange factor]]s such as [[SOS1]]. Once activated, these exchange factors can activate more small G proteins, thus amplifying the receptor's initial signal. The mutation of certain RTK genes, as with that of GPCRs, can result in the [[gene expression|expression]] of receptors that exist in a constitutively activated state; such mutated genes may act as [[oncogenes]].<ref name="roskoski">{{Cite journal |vauthors=Roskoski R |date=June 2004 |title=The ErbB/HER receptor protein-tyrosine kinases and cancer |journal=Biochemical and Biophysical Research Communications |volume=319 |issue=1 |pages=1–11 |doi=10.1016/j.bbrc.2004.04.150 |pmid=15158434}}</ref>

[[Histidine kinase|Histidine-specific protein kinases]] are structurally distinct from other protein kinases and are found in prokaryotes, fungi, and plants as part of a two-component signal transduction mechanism: a phosphate group from ATP is first added to a histidine residue within the kinase, then transferred to an aspartate residue on a receiver domain on a different protein or the kinase itself, thus activating the aspartate residue.<ref>{{Cite journal |vauthors=Wolanin PM, Thomason PA, Stock JB |date=September 2002 |title=Histidine protein kinases: key signal transducers outside the animal kingdom |journal=Genome Biology |volume=3 |issue=10 |pages=REVIEWS3013 |doi=10.1186/gb-2002-3-10-reviews3013 |pmc=244915 |pmid=12372152 |doi-access=free}}</ref>