Editing Signal transduction (section)

===Ligands===
{{Main|Ligand (biochemistry)}}
The majority of signal transduction pathways involve the binding of signaling molecules, known as ligands, to receptors that trigger events inside the cell. The binding of a signaling molecule with a receptor causes a change in the conformation of the receptor, known as ''receptor activation''. Most ligands are soluble molecules from the extracellular medium which bind to [[cell surface receptors]]. These include [[growth factors]], [[cytokines]] and [[neurotransmitters]]. Components of the [[extracellular matrix]] such as [[fibronectin]] and [[hyaluronan]] can also bind to such receptors ([[integrins]] and [[CD44]], respectively). In addition, some molecules such as [[steroid hormones]] are lipid-soluble and thus cross the plasma membrane to reach cytoplasmic or [[nuclear receptors]].<ref name="beato">{{Cite journal |vauthors=Beato M, Chávez S, Truss M |date=April 1996 |title=Transcriptional regulation by steroid hormones |journal=Steroids |volume=61 |issue=4 |pages=240–51 |doi=10.1016/0039-128X(96)00030-X |pmid=8733009 |s2cid=20654561}}</ref> In the case of [[steroid hormone receptor]]s, their stimulation leads to binding to the [[promoter (biology)|promoter region]] of steroid-responsive genes.<ref name="hammes">{{Cite journal |vauthors=Hammes SR |date=March 2003 |title=The further redefining of steroid-mediated signaling |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=100 |issue=5 |pages=2168–70 |bibcode=2003PNAS..100.2168H |doi=10.1073/pnas.0530224100 |pmc=151311 |pmid=12606724 |doi-access=free}}</ref>

Not all classifications of signaling molecules take into account the molecular nature of each class member. For example, [[odorants]] belong to a wide range of molecular classes,<ref name="ronnett">{{Cite journal |vauthors=Ronnett GV, Moon C |year=2002 |title=G proteins and olfactory signal transduction |journal=Annual Review of Physiology |volume=64 |issue=1 |pages=189–222 |doi=10.1146/annurev.physiol.64.082701.102219 |pmid=11826268}}</ref> as do neurotransmitters, which range in size from small molecules such as [[dopamine]]<ref name="missale">{{Cite journal |vauthors=Missale C, Nash SR, Robinson SW, Jaber M, Caron MG |date=January 1998 |title=Dopamine receptors: from structure to function |journal=Physiological Reviews |volume=78 |issue=1 |pages=189–225 |doi=10.1152/physrev.1998.78.1.189 |pmid=9457173}}</ref> to [[neuropeptides]] such as [[endorphins]].<ref name="goldstein">{{Cite journal |vauthors=Goldstein A |date=September 1976 |title=Opioid peptides endorphins in pituitary and brain |journal=Science |volume=193 |issue=4258 |pages=1081–6 |bibcode=1976Sci...193.1081G |doi=10.1126/science.959823 |pmid=959823}}</ref> Moreover, some molecules may fit into more than one class, e.g. [[epinephrine]] is a neurotransmitter when secreted by the [[central nervous system]] and a hormone when secreted by the [[adrenal medulla]].<ref>{{Cite web |date=2011-02-02 |title=https://www.cancer.gov/publications/dictionaries/cancer-terms/def/epinephrine |url=https://www.cancer.gov/publications/dictionaries/cancer-terms/def/epinephrine |access-date=2025-04-24 |website=www.cancer.gov |language=en}}</ref>

Some receptors such as [[HER2]] are capable of '''ligand-independent activation''' when overexpressed or mutated. This leads to constitutive activation of the pathway, which may or may not be overturned by compensation mechanisms. In the case of HER2, which acts as a dimerization partner of other [[ErbB|EGFR]]s, constitutive activation leads to hyperproliferation and [[cancer]].<ref>{{Cite journal |vauthors=Koboldt DC, Fulton RS, McLellan MD, Schmidt H, Kalicki-Veizer J, McMichael JF, etal |date=October 2012 |title=Comprehensive molecular portraits of human breast tumours |journal=Nature |volume=490 |issue=7418 |pages=61–70 |bibcode=2012Natur.490...61T |doi=10.1038/nature11412 |pmc=3465532 |pmid=23000897 |collaboration=The Cancer Genome Atlas Network}}</ref>