[Skip to Content](https://www.sigmaaldrich.com#main-content) [![MilliporeSigma](https://www.sigmaaldrich.com/static/logos/purple/millipore_sigma.svg)](https://www.sigmaaldrich.com/CA/en) Products Cart0 CAEN Products [Login / Register](https://www.sigmaaldrich.com/oidc-sign-in) [Order Lookup](https://www.sigmaaldrich.com/CA/en/order-lookup) [Quick Order](https://www.sigmaaldrich.com/CA/en/quick-order) Cart0 [Home](https://www.sigmaaldrich.com/CA/en)[Protein Expression](https://www.sigmaaldrich.com/CA/en/applications/protein-biology/protein-expression)Src Family Kinases Overview # Src Family Kinases Overview Since the isolation of v-Src as the transforming component of Rous sarcoma virus, and the subsequent identification of its cellular homolog c-Src, there has been intense interest in its activity and regulation. Src is the founding member of a group of non-receptor protein tyrosine kinases termed the Src family kinases (SFKs). All members share a basic mutidomain structure and a high degree of homology. SFKs can be further subdivided into a core group of “typical” SFKs which in humans consists of eight members (Src, Blk, Fgr, Fyn, Hck, Lck, Lyn, and Yes), a small group of atypical members (Brk, Frk and Srm), and two closely related kinases (Csk and Matk), that regulate the typical SFKs. Typical SFKs are defined by the presence of five domains: a unique region of variable length, containing at its extreme amino-terminus motifs specifying modification by the short fatty acids palmitate and/or myristate; an SH3 domain, which mediates binding to specific PXXP motifs; an SH2 domain which governs binding to specific phosphotyrosine residues; a catalytic domain containing a tyrosine in the activation loop whose phosphorylation modulates catalytic activity; and a short carboxy-terminal tail with a tyrosine residue whose phosphorylation negatively regulates the enzyme. The atypical members all share a similar core structure, although none have the motif required for myristylation, and while Frk and Brk have a regulatory tyrosine in the C-tail, Srm does not. In addition, all atypical members have a nuclear localization sequence in the SH2 domain. The regulators Csk and Matk lack myristylation motifs, activation loop tyrosines and C-terminal regulatory tails. The activity of typical SFKs is exquisitely regulated by structural constraints. They are usually held in a “closed” inactive form, and transition to an “open” active conformation upon a stimulus. For example, Src in the inactive form is phosphorylated in the C-terminal tail (tyrosine 530), a reaction usually carried out by Csk. This phosphorylation favors interaction between the tail and the SH2 domain which, together with a second intramolecular interaction between the SH3 domain and sequences linking the SH2 domain and the kinase domain, promotes the closed conformation. The SH2 and SH3 domains are masked, and the conformation of the kinase domain is unfavorable for catalysis. Transition to the active state can occur via either dephosphorylation of the tail tyrosine or by the binding of high affinity ligands to the SH2 and/or SH3 domains. SFKs are frequently activated when extracellular ligands associate with their cognate receptors (such as receptor tyrosine kinases, G-protein coupled receptors, integrin receptors and immune recognition receptors) as well as intrinsically during mitosis. SFKs participate in mitogenesis, cell survival, cytoskeletal reorganization and motility, as well as specialized functions such as immune cell development, neuronal cell signaling, osteoclast and platelet function etc. In addition, deregulation and/or overexpression of both typical and atypical SFKs have been implicated in cancer causation. In keeping with the involvement of SFKs in many signaling pathways, a large and growing number of SFK substrates are being identified (currently more than 50 for Src alone). Several small molecule inhibitors of SFKs have been identified, of which two (PP2 and SU6656) are generally available. PP2 displays considerable selectivity for SFKs and can inhibit Lck and Fyn in the nanomolar range; however it is an equally potent inhibitor of the PDGF receptor and other RTKs, as well as Tec kinases. SU6656 inhibits SFKs in the high nanomolar range, and does not inhibit the PDGF receptor or Tec, but it is very unlikely to be totally selective for SFKs. Where possible, results obtained with an SFK should be confirmed with a second inhibitor, or using other means. __The Table below contains accepted modulators and additional information. For a list of additional products, see the ["Similar Products"](https://www.sigmaaldrich.com#SimilarProducts) section below.__ __Family Members____Src____Blk____Fgr____Fyn____Hck__ __Other Names__c-Src pp60c-Src Src2 p55c-fgrp59Fyn Slk/SynJTK9 __Group__      __Molecular Weight__ __(kDa)__59.857.759.460.757.3 __Structural Data__536505529537526 __Isoforms__nSrcNot KnownNot KnownFyna, Fynb, Fyncp59Hck, p61Hck __Species__Avian (v-Src), human, monkey, mouse, *Xenopus*, rat, chorditeHuman, mouse, ratHuman, mouse, ratHuman, mouse, rat, *Xenopus*Human, monkey, mouse, rat __Domain__ __Organization__SH3-SH2-Tyr kinaseSH3-SH2-Tyr kinaseSH3-SH2-Tyr kinaseSH3-SH2-Tyr kinaseSH3-SH2-Tyr kinase __Phosphorylation__ __Sites__Ser12 Ser17 Tyr216 Tyr419 Tyr530Tyr389 Tyr501Tyr523 Tyr412Tyr531 Tyr420Tyr522 Tyr390 __Tissue__ __Expression__UbiquitousB cellsMyeloid cells B cellsUbiquitousMyeloid cells __Subcellular__ __Organization__Cytoplasm, plasma membraneCytoplasmCytoplasmCytoplasm, plasma membraneCytoplasm, plasma membrane __Binding Partners/__ __Associated Proteins__ADAM12 Csk EGFR FKHR Sam68 Paxillin WASp 14-3-3 β/γ/ε PKCε/ζBcl2 CBL PLCγ2 Ubiquitin protein ligase E3ACCR3 CD24 SLAM SHIP WASpPI3K (p85α) Fyn-binding protein SLAM SAP PaxillinWIP Abl p130Cas __Upstream__ __Activators__ErbB1; AP-1 PDGFR IR AMPK Neu Fibronectin FGR VDR PI3K/Akt/eNOS pathway LPS IFNγAML1 BSAP/PAX5 NERF/ELF-2 NFkB BSAP EBF Antigen receptor complexNegative regulaton of PP1a Chemokine signaling PMN adhesion UrokinaseCD95L NSAIDs RAFTK FAK Vav PDGFRActin __Downstream__ __Activation__EGFR Shc Dynamin Clathrin Raf-1 JAK1 STAT1/3/5 Tks5 G protein-linked receptor kinase 2 Caveolin-1Not KnownPI3K p120/130 Cbl Pyk2 p190RhoGAP RacPI3K p120/130 Cbl Pyk2Ca2+ MAPK __Activators__Growth factorsNot KnownNot KnownNot KnownNot Known __Inhibitors__PP1 PP2 SU6656Not KnownNot KnownPP1 PP2 SU6656PP1 PP2 __Physiological__ __Function__Cellular proliferation and differentiation, bone remodellingB lymphoid cell signal transductionCellular migration and adhesionSynaptic plasticity, implicated in learning and memory, cellular growthMay contribute to meutrophil migration and may regulate the degranulation process of neutrophils __Disease__ __Relevance__Embryonic development, multiple cancers, osteoporosisSome leukemiasB-cell acute lymphoblastic leukemiaNeurological disease – impaired special learningB-cell acute lymphoblastic leukemia ## Similar Products Sorry, an unexpected error has occurred Response not successful: Received status code 500 ### References 1\. Abram CL, Courtneidge SA. 2000. Src Family Tyrosine Kinases and Growth Factor Signaling. Experimental Cell Research. 254(1):1-13. [https://doi.org/10.1006/excr.1999.4732](https://doi.org/10.1006/excr.1999.4732) 2\. Boateng LR, Huttenlocher A. 2012. Spatiotemporal regulation of Src and its substrates at invadosomes. European Journal of Cell Biology. 91(11-12):878-888. [https://doi.org/10.1016/j.ejcb.2012.06.003](https://doi.org/10.1016/j.ejcb.2012.06.003) 3\. Boggon TJ, Eck MJ. 2004. Structure and regulation of Src family kinases. Oncogene. 23(48):7918-7927. [https://doi.org/10.1038/sj.onc.1208081](https://doi.org/10.1038/sj.onc.1208081) 4\. Bromann PA, Korkaya H, Courtneidge SA. 2004. The interplay between Src family kinases and receptor tyrosine kinases. Oncogene. 23(48):7957-7968. [https://doi.org/10.1038/sj.onc.1208079](https://doi.org/10.1038/sj.onc.1208079) 5\. Cole P. 2003. Protein tyrosine kinases Src and Csk: a tail's tale. Current Opinion in Chemical Biology. 7(5):580-585. [https://doi.org/10.1016/j.cbpa.2003.08.009](https://doi.org/10.1016/j.cbpa.2003.08.009) 6\. Creedon H, Brunton VG.. 2012. Src Kinase Inhibitors: Promising Cancer Therapeutics?. Crit Rev Oncog. 17(2):145-159. [https://doi.org/10.1615/critrevoncog.v17.i2.20](https://doi.org/10.1615/critrevoncog.v17.i2.20) 7\. Frame MC. 2002. Src in cancer: deregulation and consequences for cell behaviour. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 1602(2):114-130. [https://doi.org/10.1016/s0304-419x(02)00040-9](https://doi.org/10.1016/s0304-419x%2802%2900040-9) 8\. Geletu M. 2012. Mind the gap; regulation of gap junctional, intercellular communication by the SRC oncogene product and its effectors.. Anticancer Res.. 32, 4245-4250. [https://pubmed.ncbi.nlm.nih.gov/23060544/](https://pubmed.ncbi.nlm.nih.gov/23060544/) 9\. Kalia LV, Gingrich JR, Salter MW. 2004. Src in synaptic transmission and plasticity. Oncogene. 23(48):8007-8016. [https://doi.org/10.1038/sj.onc.1208158](https://doi.org/10.1038/sj.onc.1208158) 10\. Lu X, Liu X, Cao X, Jiao B. 2012. Novel Patented Src Kinase Inhibitor. CMC. 19(12):1821-1829. [https://doi.org/10.2174/092986712800099802](https://doi.org/10.2174/092986712800099802) 11\. Luttrell DK, Luttrell LM. 2004. Not so strange bedfellows: G-protein-coupled receptors and Src family kinases. Oncogene. 23(48):7969-7978. [https://doi.org/10.1038/sj.onc.1208162](https://doi.org/10.1038/sj.onc.1208162) 12\. Musumeci F, Schenone S, Brullo C, Botta M. 2012. An update on dual Src/Abl inhibitors. Future Medicinal Chemistry. 4 13\. Nagathihalli NS. 2012. Src-mediated regulation of E-cadherin and EMT in pancreatic cancer. Front Biosci. 17(7):2059. [https://doi.org/10.2741/4037](https://doi.org/10.2741/4037) 14\. Palacios EH, Weiss A. 2004. Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation. Oncogene. 23(48):7990-8000. [https://doi.org/10.1038/sj.onc.1208074](https://doi.org/10.1038/sj.onc.1208074) 15\. Playford MP, Schaller MD. 2004. The interplay between Src and integrins in normal and tumor biology. Oncogene. 23(48):7928-7946. [https://doi.org/10.1038/sj.onc.1208080](https://doi.org/10.1038/sj.onc.1208080) 16\. Serfas MS, Tyner AL. 2003. Brk, Srm, Frk, and Src42A Form a Distinct Family of Intracellular Src-Like Tyrosine Kinases. oncol res. 13(6):409-419. [https://doi.org/10.3727/096504003108748438](https://doi.org/10.3727/096504003108748438) 17\. Shupnik MA. 2004. Crosstalk between steroid receptors and the c-Src-receptor tyrosine kinase pathways: implications for cell proliferation. Oncogene. 23(48):7979-7989. [https://doi.org/10.1038/sj.onc.1208076](https://doi.org/10.1038/sj.onc.1208076) 18\. Thomas SM, Brugge JS. 1997. CELLULAR FUNCTIONS REGULATED BY SRC FAMILY KINASES. Annu. Rev. Cell Dev. Biol.. 13(1):513-609. 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