View source for Stem cell factor

{{Short description|Mammalian protein found in Homo sapiens}}
{{Infobox_gene}}
'''Stem cell factor''' (also known as '''SCF''', '''KIT-ligand''', '''KL''', or '''steel factor''') is a [[cytokine]] that binds to the c-KIT receptor ([[CD117]]). SCF can exist both as a [[transmembrane protein]] and a [[soluble protein]]. This cytokine plays an important role in [[hematopoiesis]] (formation of blood cells), [[spermatogenesis]], and [[melanogenesis]].

== Production ==
The gene encoding stem cell factor (SCF) is found on the Sl locus in mice and on chromosome 12q22-12q24 in humans.<ref name="pmid1707188">{{cite journal | vauthors = Geissler EN, Liao M, Brook JD, Martin FH, Zsebo KM, Housman DE, Galli SJ | title = Stem cell factor (SCF), a novel hematopoietic growth factor and ligand for c-kit tyrosine kinase receptor, maps on human chromosome 12 between 12q14.3 and 12qter | journal = Somat. Cell Mol. Genet. | volume = 17 | issue = 2 | pages = 207–14  | date = March 1991 | pmid = 1707188 | doi = 10.1007/BF01232978 | s2cid = 37793786 }}</ref> The soluble and transmembrane forms of the protein are formed by [[alternative splicing]] of the same RNA transcript,<ref name="pmid1705866">{{cite journal | vauthors = Flanagan JG, Chan DC, Leder P | title = Transmembrane form of the kit ligand growth factor is determined by alternative splicing and is missing in the Sld mutant | journal = Cell | volume = 64 | issue = 5 | pages = 1025–35  | date = March 1991 | pmid = 1705866 | doi = 10.1016/0092-8674(91)90326-t | s2cid = 11266238 }}</ref><ref name="pmid1724381">{{cite journal | vauthors = Anderson DM, Williams DE, Tushinski R, Gimpel S, Eisenman J, Cannizzaro LA, Aronson M, Croce CM, Huebner K, Cosman D | title = Alternate splicing of mRNAs encoding human mast cell growth factor and localization of the gene to chromosome 12q22-q24 | journal = Cell Growth Differ. | volume = 2 | issue = 8 | pages = 373–8  | date = August 1991 | pmid = 1724381 }}</ref>

[[Image:scf alternative splicing.JPG|left|thumb|250px|Figure 1: Alternative splicing of the same RNA transcript produces soluble and transmembrane forms of stem cell factor (SCF).]]

The soluble form of SCF contains a proteolytic cleavage site in exon 6. Cleavage at this site allows the extracellular portion of the protein to be released. The transmembrane form of SCF is formed by alternative splicing that excludes exon 6 (Figure 1). Both forms of SCF bind to c-KIT and are biologically active.

Soluble and transmembrane SCF is produced by [[fibroblasts]] and [[endothelial cells]]. Soluble SCF has a molecular weight of 18,5 [[kDa]] and forms a dimer. It is detected in normal human blood serum at 3.3&nbsp;ng/mL.<ref name="pmid7678995">{{cite journal | vauthors = Langley KE, Bennett LG, Wypych J, Yancik SA, Liu XD, Westcott KR, Chang DG, Smith KA, Zsebo KM | title = Soluble stem cell factor in human serum | journal = Blood | volume = 81 | issue = 3 | pages = 656–60  | date = February 1993 | pmid = 7678995 | doi =  10.1182/blood.V81.3.656.656| doi-access = free }}</ref>

== Role in development ==
SCF plays an important role in the [[hematopoiesis]] during embryonic development. Sites where hematopoiesis takes place, such as the fetal liver and bone marrow, all express SCF. Mice that do not express SCF die in utero from severe anemia. Mice that do not express the receptor for SCF (c-KIT) also die from anemia.<ref name="pmid9269751">{{cite journal | vauthors = Broudy VC | title = Stem cell factor and hematopoiesis | journal = Blood | volume = 90 | issue = 4 | pages = 1345–64  | date = August 1997 | pmid = 9269751 | doi =  10.1182/blood.V90.4.1345| doi-access = free }}</ref> SCF may serve as guidance cues that direct [[hematopoietic stem cells]] (HSCs) to their [[stem cell niche]] (the microenvironment in which a stem cell resides), and it plays an important role in HSC maintenance. Non-lethal point mutants on the c-KIT receptor can cause anemia, decreased fertility, and decreased pigmentation.<ref name="isbn0-8493-6678-X">{{cite book | vauthors = Blouin R, Bernstein A | veditors = Freedman MH, Feig SA | title = Clinical disorders and experimental models of erythropoietic failure | publisher = CRC Press | location = Boca Raton | year = 1993 | chapter = The White spotting and Steel hereditary anaemias of the mouse | isbn = 0-8493-6678-X }}</ref>

During development, the presence of the SCF also plays an important role in the localization of [[melanocytes]], cells that produce melanin and control pigmentation. In melanogenesis, melanoblasts migrate from the neural crest to their appropriate locations in the epidermis. Melanoblasts express the KIT receptor, and it is believed that SCF guides these cells to their terminal locations. SCF also regulates survival and proliferation of fully differentiated melanocytes in adults.<ref name="pmid12753403">{{cite journal | vauthors = Wehrle-Haller B | title = The role of Kit-ligand in melanocyte development and epidermal homeostasis | journal = Pigment Cell Res. | volume = 16 | issue = 3 | pages = 287–96  | date = June 2003 | pmid = 12753403 | doi = 10.1034/j.1600-0749.2003.00055.x }}</ref>

In [[spermatogenesis]], c-KIT is expressed in primordial germ cells, spermatogonia, and in primordial oocytes.<ref name="pmid11079457">{{cite journal | vauthors = Rossi P, Sette C, Dolci S, Geremia R | title = Role of c-kit in mammalian spermatogenesis | journal = J. Endocrinol. Invest. | volume = 23 | issue = 9 | pages = 609–15  | date = October 2000 | pmid = 11079457 | doi = 10.1007/bf03343784 | hdl = 2108/65858 | s2cid = 43786244 | url = https://art.torvergata.it/bitstream/2108/65858/2/Rossi-JEndocrinolInvest-2000.pdf | hdl-access = free }}</ref> It is also expressed in the primordial germ cells of females. SCF is expressed along the pathways that the germ cells use to reach their terminal destination in the body. It is also expressed in the final destinations for these cells. Like for melanoblasts, this helps guide the cells to their appropriate locations in the body.<ref name="pmid9269751"/>

== Role in hematopoiesis ==
SCF plays a role in the regulation of HSCs in the stem cell niche in the bone marrow. SCF has been shown to increase the survival of HSCs in vitro and contributes to the self-renewal and maintenance of HSCs in-vivo. HSCs at all stages of development express the same levels of the receptor for SCF ([[c-KIT]]).<ref name="pmid18381929">{{cite journal | vauthors = Kent D, Copley M, Benz C, Dykstra B, Bowie M, Eaves C | title = Regulation of hematopoietic stem cells by the steel factor/KIT signaling pathway | journal = Clin. Cancer Res. | volume = 14 | issue = 7 | pages = 1926–30  | date = April 2008 | pmid = 18381929 | doi = 10.1158/1078-0432.CCR-07-5134 | doi-access = free }}</ref> The stromal cells that surround HSCs are a component of the stem cell niche, and they release a number of ligands, including SCF.

[[Image:scf in hsc niche.JPG|left|thumb|200px|Figure 2: A diagram of a hematopoietic stem cell (HSC) inside its niche. It is adjacent to stromal cells that secrete ligands, such as stem cell factor (SCF).]]

In the bone marrow, HSCs and hematopoietic progenitor cells are adjacent to stromal cells, such as fibroblasts and [[osteoblasts]] (Figure 2). These HSCs remain in the niche by adhering to ECM proteins and to the stromal cells themselves. SCF has been shown to increase adhesion and thus may play a large role in ensuring that HSCs remain in the niche.<ref name="pmid9269751"/>

A small percentage of HSCs regularly leave the bone marrow to enter circulation and then return to their niche in the bone marrow.<ref name="pmid18256599">{{cite journal | vauthors = Méndez-Ferrer S, Lucas D, Battista M, Frenette PS | title = Haematopoietic stem cell release is regulated by circadian oscillations | journal = Nature | volume = 452 | issue = 7186 | pages = 442–7  | date = March 2008 | pmid = 18256599 | doi = 10.1038/nature06685 | bibcode = 2008Natur.452..442M | s2cid = 4403554 }}</ref> It is believed that concentration gradients of SCF, along with the chemokine [[Stromal cell-derived factor-1|SDF-1]], allow HSCs to find their way back to the niche.<ref name="pmid16888804">{{cite journal | vauthors = Nervi B, Link DC, DiPersio JF | title = Cytokines and hematopoietic stem cell mobilization | journal = J. Cell. Biochem. | volume = 99 | issue = 3 | pages = 690–705  | date = October 2006 | pmid = 16888804 | doi = 10.1002/jcb.21043 | s2cid = 40354996 | doi-access = free }}</ref>

In adult mice, the injection of the [[ACK2 anti-KIT antibody]], which binds to the c-Kit receptor and inactivates it, leads to severe problems in hematopoiesis. It causes a significant decrease in the number HSC and other hematopoietic progenitor cells in the bone marrow.<ref name="pmid1711568">{{cite journal | vauthors = Ogawa M, Matsuzaki Y, Nishikawa S, Hayashi S, Kunisada T, Sudo T, Kina T, Nakauchi H, Nishikawa S | title = Expression and function of c-kit in hemopoietic progenitor cells | journal = J. Exp. Med. | volume = 174 | issue = 1 | pages = 63–71  | date = July 1991 | pmid = 1711568 | pmc = 2118893 | doi = 10.1084/jem.174.1.63 }}</ref> This suggests that SCF and c-Kit plays an important role in hematopoietic function in adulthood. SCF also increases the survival of various hematopoietic progenitor cells, such as [[megakaryocyte]] progenitors, in vitro.<ref name="pmid7544641">{{cite journal | vauthors = Keller JR, Ortiz M, Ruscetti FW | title = Steel factor (c-kit ligand) promotes the survival of hematopoietic stem/progenitor cells in the absence of cell division | journal = Blood | volume = 86 | issue = 5 | pages = 1757–64  | date = September 1995 | pmid = 7544641 | doi =  10.1182/blood.V86.5.1757.bloodjournal8651757| doi-access = free }}</ref> In addition, it works with other cytokines to support the colony growth of BFU-E, CFU-GM, and CFU-GEMM4. Hematopoietic progenitor cells have also been shown to migrate towards a higher concentration gradient of SCF in vitro, which suggests that SCF is involved in [[chemotaxis]] for these cells.

Fetal HSCs are more sensitive to SCF than HSCs from adults. In fact, fetal HSCs in cell culture are 6 times more sensitive to SCF than adult HSCs based on the concentration that allows maximum survival.<ref name="pmid17327414">{{cite journal | vauthors = Bowie MB, Kent DG, Copley MR, Eaves CJ | title = Steel factor responsiveness regulates the high self-renewal phenotype of fetal hematopoietic stem cells | journal = Blood | volume = 109 | issue = 11 | pages = 5043–8  | date = June 2007 | pmid = 17327414 | doi = 10.1182/blood-2006-08-037770 | doi-access = free }}</ref>

== Expression in mast cells ==
[[Mast cells]] are the only terminally differentiated hematopoietic cells that express the c-Kit receptor. Mice with SCF or [[CD117#Role_in_cancer|c-Kit]] mutations have severe defects in the production of mast cells, having less than 1% of the normal levels of mast cells. Conversely, the injection of SCF increases mast cell numbers near the site of injection by over 100 times. In addition, SCF promotes mast cell adhesion, migration, proliferation, and survival.<ref name="pmid16760571">{{cite journal | vauthors = Okayama Y, Kawakami T | title = Development, migration, and survival of mast cells | journal = Immunol. Res. | volume = 34 | issue = 2 | pages = 97–115 | year = 2006 | pmid = 16760571 | pmc = 1490026 | doi = 10.1385/IR:34:2:97 }}</ref> It also promotes the release of histamine and tryptase, which are involved in the allergic response.

== Soluble and transmembrane forms ==
The presence of both soluble and transmembrane SCF is required for normal hematopoietic function.<ref name="pmid1705866"/><ref name="pmid1711207">{{cite journal | vauthors = Brannan CI, Lyman SD, Williams DE, Eisenman J, Anderson DM, Cosman D, Bedell MA, Jenkins NA, Copeland NG | title = Steel-Dickie mutation encodes a c-kit ligand lacking transmembrane and cytoplasmic domains | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 88 | issue = 11 | pages = 4671–4  | date = June 1991 | pmid = 1711207 | pmc = 51727 | doi = 10.1073/pnas.88.11.4671 | bibcode = 1991PNAS...88.4671B | doi-access = free }}</ref> Mice that produce the soluble SCF but not transmembrane SCF suffer from anemia, are sterile, and lack pigmentation. This suggests that transmembrane SCF plays a special role in vivo that is separate from that of soluble SCF.

== c-KIT receptor ==
{{main article|CD117}}

[[Image:kit expression in hematopoietic cells.JPG|right|thumb|300px|Figure 3: c-Kit expression in hematopoietic cells]]

SCF binds to the c-KIT receptor (CD 117), a [[receptor tyrosine kinase]].<ref name="pmid15526160">{{cite journal | vauthors = Rönnstrand L | title = Signal transduction via the stem cell factor receptor/c-Kit | journal = Cell. Mol. Life Sci. | volume = 61 | issue = 19–20 | pages = 2535–48  | date = October 2004 | pmid = 15526160 | doi = 10.1007/s00018-004-4189-6 | s2cid = 2602233 | pmc = 11924424 }}</ref> c-Kit is expressed in HSCs, mast cells, melanocytes, and germ cells. It is also expressed in hematopoietic progenitor cells including erythroblasts, myeloblasts, and megakaryocytes. However, with the exception of mast cells, expression decreases as these hematopoietic cells mature and c-KIT is not present when these cells are fully differentiated (Figure 3). SCF binding to c-KIT causes the receptor to homodimerize and auto-phosphorylate at tyrosine residues. The activation of c-Kit leads to the activation of multiple signaling cascades, including the RAS/ERK, PI3-Kinase, Src kinase, and JAK/STAT pathways.<ref name="pmid15526160"/>

== Clinical relevance ==

SCF may be used along with other cytokines to culture HSCs and hematopoietic progenitors. The expansion of these cells ex-vivo (outside the body) would allow advances in [[bone marrow transplantation]], in which HSCs are transferred to a patient to re-establish blood formation.<ref name="pmid18381929"/> One of the problems of injecting SCF for therapeutic purposes is that SCF activates mast cells. The injection of SCF has been shown to cause allergic-like symptoms and the proliferation of mast cells and melanocytes.<ref name="pmid9269751"/>

Cardiomyocyte-specific overexpression of transmembrane SCF promotes stem cell migration and improves cardiac function and animal survival after myocardial infarction.<ref>{{cite journal | vauthors = Xiang FL, Lu X, Hammoud L, Zhu P, Chidiac P, Robbins J, Feng Q | title = Cardiomyocyte-specific overexpression of human stem cell factor improves cardiac function and survival after myocardial infarction in mice | journal = Circulation | volume = 120 | issue = 12 | pages = 1065–74, 9 p following 1074  | date = September 2009 | pmid = 19738140 | doi = 10.1161/CIRCULATIONAHA.108.839068 | doi-access = free }}</ref>

== Interactions ==

Stem cell factor has been shown to [[Protein-protein interaction|interact]] with [[CD117]].<ref name=pmid1375232>{{cite journal | vauthors = Lev S, Yarden Y, Givol D | title = A recombinant ectodomain of the receptor for the stem cell factor (SCF) retains ligand-induced receptor dimerization and antagonizes SCF-stimulated cellular responses | journal = J. Biol. Chem. | volume = 267 | issue = 15 | pages = 10866–73  | date = May 1992 | doi = 10.1016/S0021-9258(19)50098-9 | pmid = 1375232 | doi-access = free }}</ref><ref name=pmid7680037>{{cite journal | vauthors = Blechman JM, Lev S, Brizzi MF, Leitner O, Pegoraro L, Givol D, Yarden Y | title = Soluble c-kit proteins and antireceptor monoclonal antibodies confine the binding site of the stem cell factor | journal = J. Biol. Chem. | volume = 268 | issue = 6 | pages = 4399–406  | date = Feb 1993 | doi = 10.1016/S0021-9258(18)53623-1 | pmid = 7680037 | doi-access = free }}</ref>

== References ==
{{Reflist|2}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Lennartsson J, Rönnstrand L | title = Stem cell factor receptor/c-Kit: from basic science to clinical implications | journal = Physiol. Rev. | volume = 92 | issue = 4 | pages = 1619–49 | year = 2012 | pmid = 23073628 | doi = 10.1152/physrev.00046.2011 }}
* {{cite journal | vauthors = Broudy VC | title = Stem cell factor and hematopoiesis | journal = Blood | volume = 90 | issue = 4 | pages = 1345–64 | year = 1997 | pmid = 9269751 | doi =  10.1182/blood.V90.4.1345| doi-access = free }}
* {{cite journal | vauthors = Andrews RG, Briddell RA, Appelbaum FR, McNiece IK | title = Stimulation of hematopoiesis in vivo by stem cell factor | journal = Curr. Opin. Hematol. | volume = 1 | issue = 3 | pages = 187–96 | year = 1994 | pmid = 9371281 }}
* {{cite journal | vauthors = Wehrle-Haller B | title = The role of Kit-ligand in melanocyte development and epidermal homeostasis | journal = Pigment Cell Res. | volume = 16 | issue = 3 | pages = 287–96 | year = 2003 | pmid = 12753403 | doi = 10.1034/j.1600-0749.2003.00055.x }}
* {{cite journal | vauthors = Rönnstrand L | title = Signal transduction via the stem cell factor receptor/c-Kit | journal = Cell. Mol. Life Sci. | volume = 61 | issue = 19–20 | pages = 2535–48 | year = 2004 | pmid = 15526160 | doi = 10.1007/s00018-004-4189-6 | s2cid = 2602233 | pmc = 11924424 }}
* {{cite journal | vauthors = Mroczko B, Szmitkowski M | title = Hematopoietic cytokines as tumor markers | journal = Clin. Chem. Lab. Med. | volume = 42 | issue = 12 | pages = 1347–54 | year = 2004 | pmid = 15576295 | doi = 10.1515/CCLM.2004.253 | s2cid = 11414705 }}
* {{cite journal | vauthors = Lev S, Yarden Y, Givol D | title = A recombinant ectodomain of the receptor for the stem cell factor (SCF) retains ligand-induced receptor dimerization and antagonizes SCF-stimulated cellular responses | journal = J. Biol. Chem. | volume = 267 | issue = 15 | pages = 10866–73 | year = 1992 | doi = 10.1016/S0021-9258(19)50098-9 | pmid = 1375232 | doi-access = free }}
* {{cite journal | vauthors = Huang EJ, Nocka KH, Buck J, Besmer P | title = Differential expression and processing of two cell associated forms of the kit-ligand: KL-1 and KL-2 | journal = Mol. Biol. Cell | volume = 3 | issue = 3 | pages = 349–62 | year = 1992 | pmid = 1378327 | pmc = 275535 | doi = 10.1091/mbc.3.3.349 }}
* {{cite journal | vauthors = Toyota M, Hinoda Y, Itoh F, Tsujisaki M, Imai K, Yachi A | title = Expression of two types of kit ligand mRNAs in human tumor cells | journal = Int. J. Hematol. | volume = 55 | issue = 3 | pages = 301–4 | year = 1992 | pmid = 1379846 }}
* {{cite journal | vauthors = Lu HS, Clogston CL, Wypych J, Parker VP, Lee TD, Swiderek K, Baltera RF, Patel AC, Chang DC, Brankow DW | title = Post-translational processing of membrane-associated recombinant human stem cell factor expressed in Chinese hamster ovary cells | journal = Arch. Biochem. Biophys. | volume = 298 | issue = 1 | pages = 150–8 | year = 1992 | pmid = 1381905 | doi = 10.1016/0003-9861(92)90106-7 }}
* {{cite journal | vauthors = Sharkey A, Jones DS, Brown KD, Smith SK | title = Expression of messenger RNA for kit-ligand in human placenta: localization by in situ hybridization and identification of alternatively spliced variants | journal = Mol. Endocrinol. | volume = 6 | issue = 8 | pages = 1235–41 | year = 1992 | pmid = 1383693 | doi = 10.1210/mend.6.8.1383693 | doi-access = free }}
* {{cite journal | vauthors = Mathew S, Murty VV, Hunziker W, Chaganti RS | title = Subregional mapping of 13 single-copy genes on the long arm of chromosome 12 by fluorescence in situ hybridization | journal = Genomics | volume = 14 | issue = 3 | pages = 775–9 | year = 1992 | pmid = 1427906 | doi = 10.1016/S0888-7543(05)80184-3 }}
* {{cite journal | vauthors = Geissler EN, Liao M, Brook JD, Martin FH, Zsebo KM, Housman DE, Galli SJ | title = Stem cell factor (SCF), a novel hematopoietic growth factor and ligand for c-kit tyrosine kinase receptor, maps on human chromosome 12 between 12q14.3 and 12qter | journal = Somat. Cell Mol. Genet. | volume = 17 | issue = 2 | pages = 207–14 | year = 1991 | pmid = 1707188 | doi = 10.1007/BF01232978 | s2cid = 37793786 }}
* {{cite journal | vauthors = Anderson DM, Williams DE, Tushinski R, Gimpel S, Eisenman J, Cannizzaro LA, Aronson M, Croce CM, Huebner K, Cosman D | title = Alternate splicing of mRNAs encoding human mast cell growth factor and localization of the gene to chromosome 12q22-q24 | journal = Cell Growth Differ. | volume = 2 | issue = 8 | pages = 373–8 | year = 1991 | pmid = 1724381 }}
* {{cite journal | vauthors = Martin FH, Suggs SV, Langley KE, Lu HS, Ting J, Okino KH, Morris CF, McNiece IK, Jacobsen FW, Mendiaz EA | title = Primary structure and functional expression of rat and human stem cell factor DNAs | journal = Cell | volume = 63 | issue = 1 | pages = 203–11 | year = 1990 | pmid = 2208279 | doi = 10.1016/0092-8674(90)90301-T | s2cid = 9425857 }}
* {{cite journal | vauthors = Ramenghi U, Ruggieri L, Dianzani I, Rosso C, Brizzi MF, Camaschella C, Pietsch T, Saglio G | title = Human peripheral blood granulocytes and myeloid leukemic cell lines express both transcripts encoding for stem cell factor | journal = Stem Cells | volume = 12 | issue = 5 | pages = 521–6 | year = 1994 | pmid = 7528592 | doi = 10.1002/stem.5530120508 | s2cid = 39550926 }}
* {{cite journal | vauthors = Saito S, Enomoto M, Sakakura S, Ishii Y, Sudo T, Ichijo M | title = Localization of stem cell factor (SCF) and c-kit mRNA in human placental tissue and biological effects of SCF on DNA synthesis in primary cultured cytotrophoblasts | journal = Biochem. Biophys. Res. Commun. | volume = 205 | issue = 3 | pages = 1762–9 | year = 1994 | pmid = 7529021 | doi = 10.1006/bbrc.1994.2873 }}
* {{cite journal | vauthors = Laitinen M, Rutanen EM, Ritvos O | title = Expression of c-kit ligand messenger ribonucleic acids in human ovaries and regulation of their steady state levels by gonadotropins in cultured granulosa-luteal cells | journal = Endocrinology | volume = 136 | issue = 10 | pages = 4407–14 | year = 1995 | pmid = 7545103 | doi = 10.1210/endo.136.10.7545103 }}
* {{cite journal | vauthors = Blechman JM, Lev S, Brizzi MF, Leitner O, Pegoraro L, Givol D, Yarden Y | title = Soluble c-kit proteins and antireceptor monoclonal antibodies confine the binding site of the stem cell factor | journal = J. Biol. Chem. | volume = 268 | issue = 6 | pages = 4399–406 | year = 1993 | doi = 10.1016/S0021-9258(18)53623-1 | pmid = 7680037 | doi-access = free }}
* {{cite journal | vauthors = Lu HS, Jones MD, Shieh JH, Mendiaz EA, Feng D, Watler P, Narhi LO, Langley KE | title = Isolation and characterization of a disulfide-linked human stem cell factor dimer. Biochemical, biophysical, and biological comparison to the noncovalently held dimer | journal = J. Biol. Chem. | volume = 271 | issue = 19 | pages = 11309–16 | year = 1996 | pmid = 8626683 | doi = 10.1074/jbc.271.19.11309 | doi-access = free }}
* {{cite journal | vauthors = Vanhaesebroeck B, [[Melanie Welham|Welham MJ]], Kotani K, Stein R, Warne PH, Zvelebil MJ, Higashi K, Volinia S, Downward J, Waterfield MD | title = P110delta, a novel phosphoinositide 3-kinase in leukocytes | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 94 | issue = 9 | pages = 4330–5 | year = 1997 | pmid = 9113989 | pmc = 20722 | doi = 10.1073/pnas.94.9.4330 | bibcode = 1997PNAS...94.4330V | doi-access = free }}
{{refend}}

== External links ==
* {{MeshName|Stem+cell+factor}}
* https://www.genome.jp/dbget-bin/show_pathway?hsa04640+4254 - KEGG pathway: Hematopoietic cell lineage

{{PDB Gallery|geneid=4254}}
{{Growth factors}}
{{Cytokines}}
{{Growth factor receptor modulators}}
{{Cytokine receptor modulators}}