Signaling by SCF-KIT (Homo sapiens)

From WikiPathways

Revision as of 10:02, 11 June 2014 by ReactomeTeam (Talk | contribs)
Jump to: navigation, search
18, 35, 44, 56, 64...44, 61, 642, 16, 44, 454824, 29, 512929, 516, 25, 33, 34, 50...5, 33, 60, 64232712, 19, 46, 538, 32, 33, 65, 689, 31, 4143415215, 54464, 14, 40, 4833, 62, 6821, 30, 337, 11, 17, 3728, 4838, 58412942, 5826, 434337, 5520, 33, 34, 49, 681, 3, 7, 13, 22...47, 59SFKsp-KIT complex sSCF dimer p-APS dimerp-KIT complex Src family tyrosine kinases SFKsp-KIT complex SFKsp-KIT complex Src family tyrosine kinases Src family tyrosine kinases Src family tyrosine kinases APS dimer STATs SFKsp-KIT complex Src family tyrosine kinases p-7Y-KITsSCF dimerp-7Y-KIT SFKsp-KIT complex sSCF dimer p-7Y-KITsSCF dimerp-7Y-KIT p-7Y-KITsSCF dimerp-7Y-KIT JAK2SFKSp-KIT complex cytosolp-7Y-KITsSCF dimerp-7Y-KIT SFKsp-KIT complex sSCF dimer sSCF dimer p-7Y-KITsSCF dimerp-7Y-KIT p-7Y-KITsSCF dimerp-7Y-KIT RAC1-GTP sSCF dimer sSCF dimer SFKsp-KIT complex Tyrosine kinasesp-KIT complex sSCF dimer SFKsp-KIT complex p-7Y-KITsSCF dimerp-7Y-KIT GAB2GRB2p-SHP2p-KIT complex p-JAK2SFKsp-KIT complex P13KpsSCF dimer sSCF dimer Src family tyrosine kinases PI3K alpha sSCF dimer sSCF dimer sSCF dimer p-7Y-KITsSCF dimerp-7Y-KIT SFKsp-8Y-KITsSCF dimerp-8Y-KIT p-SHP2p-KIT complex Src family tyrosine kinases p-STAT dimers GRB2p-SHP2p-KIT complex sSCF dimer p21 RAS p-8Y-KITsSCF dimerp-8Y-KIT p-STATs pSFKsp-KIT complex SHP2SFKsp-KITsSCF dimerp-KIT sSCF dimer Src family tyrosine kinases p21 RASGTP PI3Kp-KITsSCF dimerp-KIT p-7Y-KITsSCF dimerp-7Y-KIT p-7Y-KITsSCF dimerp-7Y-KIT Src family tyrosine kinases APS dimerp-c-KitSFKs complex Src family tyrosine kinases p-7Y-KITsSCF dimerp-7Y-KIT p-VAV1PIP3 sSCF dimer GRB2p-SHP2p-KIT complex sSCF dimer p-7Y-KITsSCF dimerp-7Y-KIT PI3K alpha SOCS1p-KIT complex p-7Y-KITsSCF dimerp-7Y-KIT Src family tyrosine kinases sSCF dimer GRB2SOS1 KITsSCF dimerKIT nucleoplasmsSCF dimer sSCF dimer GRB2SOS1p-KIT complex p-7Y-KITsSCF dimerp-7Y-KIT SFKsp-KIT complex p-7Y-KITsSCF dimerp-7Y-KIT sSCF dimer p-JAK2SFKsp-KIT complexSTATs sSCF dimer GRB2p-SHP2p-KIT complex p-STAT dimer p-APS dimer SFKsp-KIT complex Src family tyrosine kinases p-7Y-KITsSCF dimerp-7Y-KIT Adapter proteins p-JAK2SFKsp-KIT complexp-STAT dimers p-7Y-KITsSCF dimerp-7Y-KIT Src family tyrosine kinases p-SHP2p-KIT complex KITsSCF dimer p-7Y-KITsSCF dimerp-7Y-KIT CBLGrb2/p-APSp-c-Kit complex SHP-1p-c-Kit complex GRB2SOS1 p-JAK2SFKsp-KIT complexp-STATs GRB2SOS1p-KIT complex p-APS dimerp-KIT complex p-STATs sSCF dimer p-7Y-KITsSCF dimerp-7Y-KIT SFKsp-KIT complex PI3K alpha APS dimer p21 RAS SFKsp-KIT complex RAC1-GDP sSCF dimer GRB2p-SHP2p-KIT complex p-7Y-KITsSCF dimerp-7Y-KIT sSCF dimer PTPROKIT p-7Y-KITsSCF dimerp-7Y-KIT p-SHP2p-KIT complex p-KIT Src family tyrosine kinases SFKsp-KIT complex sSCF dimer p21 RASGDP Grb2SOSp-c-Kit/p-APSp-c-Kit complex Src family tyrosine kinases Tyrosine kinases p-7Y-KITsSCF dimerp-7Y-KIT p-SHP2p-KIT complex sSCF dimer LNKp-7Y-KITsSCF dimerp-7Y-KIT sSCF dimer SOCS6p-c-KitsSCF dimerp-c-Kit p-APS dimer SFKsp-KIT complex GRB2SOS1 Adapter proteinsp-KIT complex p-STATs sSCF dimer p-7Y-KITsSCF dimerp-7Y-KIT p-7Y-KITsSCF dimerp-7Y-KIT Src family tyrosine kinases p-SHP2p-KIT complex LCK p-7Y-KIT SFKsp-8Y-KITsSCF dimerp-8Y-KITYES1p-Y694-STAT5A ATPPIK3CA SOCS1SRC-1 GAB2GRB2p-SHP2p-KIT complexGRB2SOS1p-Y701-STAT1-1 sSCF dimerLYNKITLG-1KITLG-1p-Y1007-JAK2 p-JAK2SFKsp-KIT complexSTATsNRAS KITLG-1YES1VAV1FYNp-Y701-STAT1-1 GDP FER KIT LCK PIRAF/MAP kinase cascadeLYNAPS dimerp-c-KitSFKs complexp-Y1007-JAK2 p-7Y-KIT KITLG-1PTPN6 p-Y629-SH2B2 ATPGRB2-1p-Y1007-JAK2 SRC-1 LCK SH2B2 SOCS1p-KIT complexSTATsFYNGAB2 p-Y546,Y584-PTPN11 FYNPTPN11FYNKITLG-1YES1KITLG-1p-7Y-KIT p-7Y-KIT p-7Y-KIT KITLG-1SRC-1 HRASPI3Kp-KITsSCF dimerp-KITpp-Y1007-JAK2 ATPp-7Y-KIT KITLG-1p-JAK2SFKsp-KIT complexp-STATsAPS dimerGRB10 SRC-1 SRC-1 GDPYES1LNKp-7Y-KITsSCF dimerp-7Y-KITFYNGRB2-1 SH2B3 GRB2-1 KITLG-1p-7Y-KIT Adapter proteinsp-KIT complexFYNp-Y705-STAT3 PTPRUp-VAV1PIP3GRAP2 KITLG-1SH2B2 KITLG-1p-7Y-KIT SOCS6p-c-KitsSCF dimerp-c-KitKITLG-1Adapter proteinsp-Y694-STAT5A LCK YES1RAC1 ADPPRKCAPTPRULYNp-APS dimerp-KIT complexp-7Y-KIT GRB2-1 FYNp-7Y-KIT LCK KITsSCF dimerFYNp-7Y-KIT p-Y546,Y584-PTPN11 CHEK1 LYNSRC-1 p-7Y-KIT p-7Y-KIT p-SHP2p-KIT complexLYNKIT p21 RASGDPSRC-1 LYNFYNKITLG-1JAK2STAT5A PRKCA KITLG-1ADPGRB7 STAT3 Endopeptidases for SCF processingADPSOCS6 JAK2SFKSp-KIT complexYES1p-JAK2SFKsp-KIT complexp-STAT dimersp-STAT dimersLYNFYNADPATPPTPROKITFYNp-7Y-KIT SHP2SFKsp-KITsSCF dimerp-KITSRC-1 Tyrosine kinasesp-KIT complexp-7Y-KITsSCF dimerp-7Y-KITRAC1 LYNLYNKITLG-1p-KIT LCK ATPKITLG-1LCK p-Y694-STAT5A RAC1-GTPATPGRB2SOS1p-KIT complexTEC KITLG-1SOCS1 KIT GRB2-1 PIP3 activates AKT signalingp-7Y-KIT LCK KITLG-1KITLG-1YES1p-Y705-STAT3 STAT1 KITLG-1SOS1 JAK2 SRC-1 GRB2-1 KITLG-1GTPSRC-1 CBLGrb2/p-APSp-c-Kit complexp-Y629-SH2B2 FYNLYNRAC1-GDPGTP KITLG-1SRC-1 SOS1 LCK p21 RASGTPYES1LCK PIK3CA P13Kpp-7Y-KIT p-Y-GAB2 LYNFES NRAS YES1GDP KITLG-1SHP-1p-c-Kit complexp-S741,S746-KIT ADPTyrosine kinasesGrb2SOSp-c-Kit/p-APSp-c-Kit complexYES1LCK GDPFYNp-7Y-KIT LCK Src family tyrosine kinases p-8Y-KIT KITLG-1CBL PIKITLG-1GAB2PISRC-1 p-Y705-STAT3 LYNKITLG-1SFKsp-KIT complexADPKRASp-Y546,Y584-PTPN11 GRB2-1 FYNYES1KITLG-1p-Y701-STAT1-1 PI3K alphaSOCS6KITLG-1p-JAK2SFKsp-KIT complexPIK3CA KITLG-1p-Y546,Y584-PTPN11 FYNGTPLYNp-Y142,Y160,Y174-VAV1 HRASGRB2p-SHP2p-KIT complexKRASp-7Y-KIT YES1CBLYES1PTPN6LCK FYNp-7Y-KIT GRAP p-Y699-STAT5B SRC-1 SH2B3SRC-1 ATPKITYES1KITsSCF dimerKITp-7Y-KIT LYNSRC-1 YES1KITLG-1LYNp-Y699-STAT5B LYNp-Y699-STAT5B ADPSRC-1 SOS1 GRB2-1 LCK ADPp-7Y-KIT p-7Y-KIT LCK STAT5B PTPN11 p-7Y-KIT p-7Y-KIT GTP LCK p-Y546,Y584-PTPN11 KITLG-1p-Y-GAB2 YES110, 36


Description

Stem cell factor (SCF) is a growth factor with membrane bound and soluble forms. It is expressed by fibroblasts and endothelial cells throughout the body, promoting proliferation, migration, survival and differentiation of hematopoetic progenitors, melanocytes and germ cells.(Linnekin 1999, Rönnstrand 2004, Lennartsson and Rönnstrand 2006). The receptor for SCF is KIT, a tyrosine kinase receptor (RTK) closely related to the receptors for platelet derived growth factor receptor, colony stimulating factor 1 (Linnekin 1999) and Flt3 (Rosnet et al. 1991). Four isoforms of c-Kit have been identified in humans. Alternative splicing results in isoforms of KIT differing in the presence or absence of four residues (GNNK) in the extracellular region. This occurs due to the use of an alternate 5' splice donor site. These GNNK+ and GNNK- variants are co-expressed in most tissues; the GNNK- form predominates and was more strongly tyrosine-phosphorylated and more rapidly internalized (Rönnstrand 2004). There are also splice variants that arise from alternative usage of splice acceptor site resulting in the presence or absence of a serine residue (Crosier et al., 1993). Finally, there is an alternative shorter transcript of KIT expressed in postmeiotic germ cells in the testis which encodes a truncated KIT consisting only of the second part of the kinase domain and thus lackig the extracellular and transmembrane domains as well as the first part of the kinase domain (Rossi et al. 1991). Binding of SCF homodimers to KIT results in KIT homodimerization followed by activation of its intrinsic tyrosine kinase activity. KIT stimulation activates a wide array of signalling pathways including MAPK, PI3K and JAK/STAT (Reber et al. 2006, Rönnstrand 2004). Defects of KIT in humans are associated with different genetic diseases and also in several types of cancers like mast cell leukaemia, germ cell tumours, certain subtypes of malignant melanoma and gastrointestinal tumours. Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=1433557

Quality Tags

Ontology Terms

 

Bibliography

View all...
  1. McKay MM, Morrison DK.; ''Integrating signals from RTKs to ERK/MAPK.''; PubMed Europe PMC Scholia
  2. Caruana G, Cambareri AC, Ashman LK.; ''Isoforms of c-KIT differ in activation of signalling pathways and transformation of NIH3T3 fibroblasts.''; PubMed Europe PMC Scholia
  3. Lemmon MA, Pinchasi D, Zhou M, Lax I, Schlessinger J.; ''Kit receptor dimerization is driven by bivalent binding of stem cell factor.''; PubMed Europe PMC Scholia
  4. Miyazawa K, Hendrie PC, Mantel C, Wood K, Ashman LK, Broxmeyer HE.; ''Comparative analysis of signaling pathways between mast cell growth factor (c-kit ligand) and granulocyte-macrophage colony-stimulating factor in a human factor-dependent myeloid cell line involves phosphorylation of Raf-1, GTPase-activating protein and mitogen-activated protein kinase.''; PubMed Europe PMC Scholia
  5. Feng J, Witthuhn BA, Matsuda T, Kohlhuber F, Kerr IM, Ihle JN.; ''Activation of Jak2 catalytic activity requires phosphorylation of Y1007 in the kinase activation loop.''; PubMed Europe PMC Scholia
  6. Thömmes K, Lennartsson J, Carlberg M, Rönnstrand L.; ''Identification of Tyr-703 and Tyr-936 as the primary association sites for Grb2 and Grb7 in the c-Kit/stem cell factor receptor.''; PubMed Europe PMC Scholia
  7. Tang B, Mano H, Yi T, Ihle JN.; ''Tec kinase associates with c-kit and is tyrosine phosphorylated and activated following stem cell factor binding.''; PubMed Europe PMC Scholia
  8. Blume-Jensen P, Wernstedt C, Heldin CH, Rönnstrand L.; ''Identification of the major phosphorylation sites for protein kinase C in kit/stem cell factor receptor in vitro and in intact cells.''; PubMed Europe PMC Scholia
  9. Jhun BH, Rivnay B, Price D, Avraham H.; ''The MATK tyrosine kinase interacts in a specific and SH2-dependent manner with c-Kit.''; PubMed Europe PMC Scholia
  10. Masuhara M, Nagao K, Nishikawa M, Sasaki M, Yoshimura A, Osawa M.; ''Molecular cloning of murine STAP-1, the stem-cell-specific adaptor protein containing PH and SH2 domains.''; PubMed Europe PMC Scholia
  11. Cseh B, Doma E, Baccarini M.; ''"RAF" neighborhood: protein-protein interaction in the Raf/Mek/Erk pathway.''; PubMed Europe PMC Scholia
  12. Brown MD, Sacks DB.; ''Protein scaffolds in MAP kinase signalling.''; PubMed Europe PMC Scholia
  13. Lennartsson J, Blume-Jensen P, Hermanson M, Pontén E, Carlberg M, Rönnstrand L.; ''Phosphorylation of Shc by Src family kinases is necessary for stem cell factor receptor/c-kit mediated activation of the Ras/MAP kinase pathway and c-fos induction.''; PubMed Europe PMC Scholia
  14. Turjanski AG, Vaqué JP, Gutkind JS.; ''MAP kinases and the control of nuclear events.''; PubMed Europe PMC Scholia
  15. Vanhaesebroeck B, Leevers SJ, Ahmadi K, Timms J, Katso R, Driscoll PC, Woscholski R, Parker PJ, Waterfield MD.; ''Synthesis and function of 3-phosphorylated inositol lipids.''; PubMed Europe PMC Scholia
  16. Gueller S, Gery S, Nowak V, Liu L, Serve H, Koeffler HP.; ''Adaptor protein Lnk associates with Tyr(568) in c-Kit.''; PubMed Europe PMC Scholia
  17. Tauchi T, Feng GS, Marshall MS, Shen R, Mantel C, Pawson T, Broxmeyer HE.; ''The ubiquitously expressed Syp phosphatase interacts with c-kit and Grb2 in hematopoietic cells.''; PubMed Europe PMC Scholia
  18. Wollberg P, Lennartsson J, Gottfridsson E, Yoshimura A, Rönnstrand L.; ''The adapter protein APS associates with the multifunctional docking sites Tyr-568 and Tyr-936 in c-Kit.''; PubMed Europe PMC Scholia
  19. Masson K, Heiss E, Band H, Rönnstrand L.; ''Direct binding of Cbl to Tyr568 and Tyr936 of the stem cell factor receptor/c-Kit is required for ligand-induced ubiquitination, internalization and degradation.''; PubMed Europe PMC Scholia
  20. Roberts PJ, Der CJ.; ''Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer.''; PubMed Europe PMC Scholia
  21. Yuzawa S, Opatowsky Y, Zhang Z, Mandiyan V, Lax I, Schlessinger J.; ''Structural basis for activation of the receptor tyrosine kinase KIT by stem cell factor.''; PubMed Europe PMC Scholia
  22. Chardin P, Camonis JH, Gale NW, van Aelst L, Schlessinger J, Wigler MH, Bar-Sagi D.; ''Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2.''; PubMed Europe PMC Scholia
  23. Piao X, Curtis JE, Minkin S, Minden MD, Bernstein A.; ''Expression of the Kit and KitA receptor isoforms in human acute myelogenous leukemia.''; PubMed Europe PMC Scholia
  24. Fukumoto T, Kubota Y, Kitanaka A, Yamaoka G, Ohara-Waki F, Imataki O, Ohnishi H, Ishida T, Tanaka T.; ''Gab1 transduces PI3K-mediated erythropoietin signals to the Erk pathway and regulates erythropoietin-dependent proliferation and survival of erythroid cells.''; PubMed Europe PMC Scholia
  25. Masson K, Rönnstrand L.; ''Oncogenic signaling from the hematopoietic growth factor receptors c-Kit and Flt3.''; PubMed Europe PMC Scholia
  26. Broudy VC, Lin NL, Bühring HJ, Komatsu N, Kavanagh TJ.; ''Analysis of c-kit receptor dimerization by fluorescence resonance energy transfer.''; PubMed Europe PMC Scholia
  27. Matous JV, Langley K, Kaushansky K.; ''Structure-function relationships of stem cell factor: an analysis based on a series of human-murine stem cell factor chimera and the mapping of a neutralizing monoclonal antibody.''; PubMed Europe PMC Scholia
  28. Yi T, Ihle JN.; ''Association of hematopoietic cell phosphatase with c-Kit after stimulation with c-Kit ligand.''; PubMed Europe PMC Scholia
  29. Ross D, Joyner WL.; ''Resting distribution and stimulated translocation of protein kinase C isoforms alpha, epsilon and zeta in response to bradykinin and TNF in human endothelial cells.''; PubMed Europe PMC Scholia
  30. Blechman JM, Lev S, Brizzi MF, Leitner O, Pegoraro L, Givol D, Yarden Y.; ''Soluble c-kit proteins and antireceptor monoclonal antibodies confine the binding site of the stem cell factor.''; PubMed Europe PMC Scholia
  31. Mendiaz EA, Chang DG, Boone TC, Grant JR, Wypych J, Aguero B, Egrie JC, Langley KE.; ''Epitope mapping and immunoneutralization of recombinant human stem-cell factor.''; PubMed Europe PMC Scholia
  32. Craig AW, Greer PA.; ''Fer kinase is required for sustained p38 kinase activation and maximal chemotaxis of activated mast cells.''; PubMed Europe PMC Scholia
  33. Lev S, Yarden Y, Givol D.; ''A recombinant ectodomain of the receptor for the stem cell factor (SCF) retains ligand-induced receptor dimerization and antagonizes SCF-stimulated cellular responses.''; PubMed Europe PMC Scholia
  34. Feng GS, Ouyang YB, Hu DP, Shi ZQ, Gentz R, Ni J.; ''Grap is a novel SH3-SH2-SH3 adaptor protein that couples tyrosine kinases to the Ras pathway.''; PubMed Europe PMC Scholia
  35. Deberry C, Mou S, Linnekin D.; ''Stat1 associates with c-kit and is activated in response to stem cell factor.''; PubMed Europe PMC Scholia
  36. Serve H, Hsu YC, Besmer P.; ''Tyrosine residue 719 of the c-kit receptor is essential for binding of the P85 subunit of phosphatidylinositol (PI) 3-kinase and for c-kit-associated PI 3-kinase activity in COS-1 cells.''; PubMed Europe PMC Scholia
  37. Crespo P, Schuebel KE, Ostrom AA, Gutkind JS, Bustelo XR.; ''Phosphotyrosine-dependent activation of Rac-1 GDP/GTP exchange by the vav proto-oncogene product.''; PubMed Europe PMC Scholia
  38. Lennartsson J, Rönnstrand L.; ''The stem cell factor receptor/c-Kit as a drug target in cancer.''; PubMed Europe PMC Scholia
  39. Roskoski R.; ''MEK1/2 dual-specificity protein kinases: structure and regulation.''; PubMed Europe PMC Scholia
  40. Chian R, Young S, Danilkovitch-Miagkova A, Rönnstrand L, Leonard E, Ferrao P, Ashman L, Linnekin D.; ''Phosphatidylinositol 3 kinase contributes to the transformation of hematopoietic cells by the D816V c-Kit mutant.''; PubMed Europe PMC Scholia
  41. Rönnstrand L.; ''Signal transduction via the stem cell factor receptor/c-Kit.''; PubMed Europe PMC Scholia
  42. Roskoski R.; ''Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor.''; PubMed Europe PMC Scholia
  43. Taniguchi Y, London R, Schinkmann K, Jiang S, Avraham H.; ''The receptor protein tyrosine phosphatase, PTP-RO, is upregulated during megakaryocyte differentiation and Is associated with the c-Kit receptor.''; PubMed Europe PMC Scholia
  44. Rao N, Dodge I, Band H.; ''The Cbl family of ubiquitin ligases: critical negative regulators of tyrosine kinase signaling in the immune system.''; PubMed Europe PMC Scholia
  45. Lennartsson J, Wernstedt C, Engström U, Hellman U, Rönnstrand L.; ''Identification of Tyr900 in the kinase domain of c-Kit as a Src-dependent phosphorylation site mediating interaction with c-Crk.''; PubMed Europe PMC Scholia
  46. Plotnikov A, Zehorai E, Procaccia S, Seger R.; ''The MAPK cascades: signaling components, nuclear roles and mechanisms of nuclear translocation.''; PubMed Europe PMC Scholia
  47. Koyasu S.; ''The role of PI3K in immune cells.''; PubMed Europe PMC Scholia
  48. Yu M, Luo J, Yang W, Wang Y, Mizuki M, Kanakura Y, Besmer P, Neel BG, Gu H.; ''The scaffolding adapter Gab2, via Shp-2, regulates kit-evoked mast cell proliferation by activating the Rac/JNK pathway.''; PubMed Europe PMC Scholia
  49. Jahn T, Seipel P, Urschel S, Peschel C, Duyster J.; ''Role for the adaptor protein Grb10 in the activation of Akt.''; PubMed Europe PMC Scholia
  50. Weiler SR, Mou S, DeBerry CS, Keller JR, Ruscetti FW, Ferris DK, Longo DL, Linnekin D.; ''JAK2 is associated with the c-kit proto-oncogene product and is phosphorylated in response to stem cell factor.''; PubMed Europe PMC Scholia
  51. Brizzi MF, Dentelli P, Lanfrancone L, Rosso A, Pelicci PG, Pegoraro L.; ''Discrete protein interactions with the Grb2/c-Cbl complex in SCF- and TPO-mediated myeloid cell proliferation.''; PubMed Europe PMC Scholia
  52. Cargnello M, Roux PP.; ''Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases.''; PubMed Europe PMC Scholia
  53. Alai M, Mui AL, Cutler RL, Bustelo XR, Barbacid M, Krystal G.; ''Steel factor stimulates the tyrosine phosphorylation of the proto-oncogene product, p95vav, in human hemopoietic cells.''; PubMed Europe PMC Scholia
  54. Cantwell-Dorris ER, O'Leary JJ, Sheils OM.; ''BRAFV600E: implications for carcinogenesis and molecular therapy.''; PubMed Europe PMC Scholia
  55. Duronio V, Welham MJ, Abraham S, Dryden P, Schrader JW.; ''p21ras activation via hemopoietin receptors and c-kit requires tyrosine kinase activity but not tyrosine phosphorylation of p21ras GTPase-activating protein.''; PubMed Europe PMC Scholia
  56. Philo JS, Wen J, Wypych J, Schwartz MG, Mendiaz EA, Langley KE.; ''Human stem cell factor dimer forms a complex with two molecules of the extracellular domain of its receptor, Kit.''; PubMed Europe PMC Scholia
  57. Roskoski R.; ''ERK1/2 MAP kinases: structure, function, and regulation.''; PubMed Europe PMC Scholia
  58. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JW, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR, Futreal PA.; ''Mutations of the BRAF gene in human cancer.''; PubMed Europe PMC Scholia
  59. Price DJ, Rivnay B, Fu Y, Jiang S, Avraham S, Avraham H.; ''Direct association of Csk homologous kinase (CHK) with the diphosphorylated site Tyr568/570 of the activated c-KIT in megakaryocytes.''; PubMed Europe PMC Scholia
  60. Mol CD, Lim KB, Sridhar V, Zou H, Chien EY, Sang BC, Nowakowski J, Kassel DB, Cronin CN, McRee DE.; ''Structure of a c-kit product complex reveals the basis for kinase transactivation.''; PubMed Europe PMC Scholia
  61. Zhang Z, Zhang R, Joachimiak A, Schlessinger J, Kong XP.; ''Crystal structure of human stem cell factor: implication for stem cell factor receptor dimerization and activation.''; PubMed Europe PMC Scholia
  62. Kyriakis JM, Avruch J.; ''Mammalian MAPK signal transduction pathways activated by stress and inflammation: a 10-year update.''; PubMed Europe PMC Scholia
  63. Hafizi S, Dahlbäck B.; ''Signalling and functional diversity within the Axl subfamily of receptor tyrosine kinases.''; PubMed Europe PMC Scholia
  64. Longley BJ, Tyrrell L, Ma Y, Williams DA, Halaban R, Langley K, Lu HS, Schechter NM.; ''Chymase cleavage of stem cell factor yields a bioactive, soluble product.''; PubMed Europe PMC Scholia
  65. Roskoski R.; ''RAF protein-serine/threonine kinases: structure and regulation.''; PubMed Europe PMC Scholia
  66. Wellbrock C, Karasarides M, Marais R.; ''The RAF proteins take centre stage.''; PubMed Europe PMC Scholia
  67. Kawaguchi N, Horiuchi K, Becherer JD, Toyama Y, Besmer P, Blobel CP.; ''Different ADAMs have distinct influences on Kit ligand processing: phorbol-ester-stimulated ectodomain shedding of Kitl1 by ADAM17 is reduced by ADAM19.''; PubMed Europe PMC Scholia
  68. Timokhina I, Kissel H, Stella G, Besmer P.; ''Kit signaling through PI 3-kinase and Src kinase pathways: an essential role for Rac1 and JNK activation in mast cell proliferation.''; PubMed Europe PMC Scholia
  69. Liu H, Chen X, Focia PJ, He X.; ''Structural basis for stem cell factor-KIT signaling and activation of class III receptor tyrosine kinases.''; PubMed Europe PMC Scholia
  70. Nicholson PR, Empereur S, Glover HR, Dilworth SM.; ''ShcA tyrosine phosphorylation sites can replace ShcA binding in signalling by middle T-antigen.''; PubMed Europe PMC Scholia
  71. Argetsinger LS, Kouadio JL, Steen H, Stensballe A, Jensen ON, Carter-Su C.; ''Autophosphorylation of JAK2 on tyrosines 221 and 570 regulates its activity.''; PubMed Europe PMC Scholia
  72. Kozlowski M, Larose L, Lee F, Le DM, Rottapel R, Siminovitch KA.; ''SHP-1 binds and negatively modulates the c-Kit receptor by interaction with tyrosine 569 in the c-Kit juxtamembrane domain.''; PubMed Europe PMC Scholia
  73. Wakioka T, Sasaki A, Mitsui K, Yokouchi M, Inoue A, Komiya S, Yoshimura A.; ''APS, an adaptor protein containing Pleckstrin homology (PH) and Src homology-2 (SH2) domains inhibits the JAK-STAT pathway in collaboration with c-Cbl.''; PubMed Europe PMC Scholia
  74. Reber L, Da Silva CA, Frossard N.; ''Stem cell factor and its receptor c-Kit as targets for inflammatory diseases.''; PubMed Europe PMC Scholia
  75. Ning ZQ, Li J, McGuinness M, Arceci RJ.; ''STAT3 activation is required for Asp(816) mutant c-Kit induced tumorigenicity.''; PubMed Europe PMC Scholia
  76. Sun J, Pedersen M, Rönnstrand L.; ''Gab2 is involved in differential phosphoinositide 3-kinase signaling by two splice forms of c-Kit.''; PubMed Europe PMC Scholia
  77. Sun J, Pedersen M, Bengtsson S, Rönnstrand L.; ''Grb2 mediates negative regulation of stem cell factor receptor/c-Kit signaling by recruitment of Cbl.''; PubMed Europe PMC Scholia
  78. Argetsinger LS, Stuckey JA, Robertson SA, Koleva RI, Cline JM, Marto JA, Myers MG, Carter-Su C.; ''Tyrosines 868, 966, and 972 in the kinase domain of JAK2 are autophosphorylated and required for maximal JAK2 kinase activity.''; PubMed Europe PMC Scholia
  79. Edling CE, Hallberg B.; ''c-Kit--a hematopoietic cell essential receptor tyrosine kinase.''; PubMed Europe PMC Scholia
  80. Crosier PS, Ricciardi ST, Hall LR, Vitas MR, Clark SC, Crosier KE.; ''Expression of isoforms of the human receptor tyrosine kinase c-kit in leukemic cell lines and acute myeloid leukemia.''; PubMed Europe PMC Scholia
  81. Heissig B, Hattori K, Dias S, Friedrich M, Ferris B, Hackett NR, Crystal RG, Besmer P, Lyden D, Moore MA, Werb Z, Rafii S.; ''Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand.''; PubMed Europe PMC Scholia
  82. Blume-Jensen P, Rönnstrand L, Gout I, Waterfield MD, Heldin CH.; ''Modulation of Kit/stem cell factor receptor-induced signaling by protein kinase C.''; PubMed Europe PMC Scholia
  83. Liu SK, McGlade CJ.; ''Gads is a novel SH2 and SH3 domain-containing adaptor protein that binds to tyrosine-phosphorylated Shc.''; PubMed Europe PMC Scholia
  84. Brizzi MF, Dentelli P, Rosso A, Yarden Y, Pegoraro L.; ''STAT protein recruitment and activation in c-Kit deletion mutants.''; PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
101337view11:22, 1 November 2018ReactomeTeamreactome version 66
100875view20:56, 31 October 2018ReactomeTeamreactome version 65
100416view19:30, 31 October 2018ReactomeTeamreactome version 64
99966view16:14, 31 October 2018ReactomeTeamreactome version 63
99520view14:49, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99162view12:41, 31 October 2018ReactomeTeamreactome version 62
93973view13:49, 16 August 2017ReactomeTeamreactome version 61
93574view11:27, 9 August 2017ReactomeTeamreactome version 61
87186view08:05, 19 July 2016EgonwOntology Term : 'signaling pathway' added !
86676view09:23, 11 July 2016ReactomeTeamreactome version 56
83115view10:00, 18 November 2015ReactomeTeamVersion54
81455view12:59, 21 August 2015ReactomeTeamVersion53
76929view08:20, 17 July 2014ReactomeTeamFixed remaining interactions
76634view12:00, 16 July 2014ReactomeTeamFixed remaining interactions
75964view10:02, 11 June 2014ReactomeTeamRe-fixing comment source
75667view10:57, 10 June 2014ReactomeTeamReactome 48 Update
75022view13:53, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74666view08:43, 30 April 2014ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ADPMetaboliteCHEBI:16761 (ChEBI)
APS dimer

p-c-Kit

SFKs complex
ComplexREACT_111288 (Reactome)
APS dimerComplexREACT_111367 (Reactome)
ATPMetaboliteCHEBI:15422 (ChEBI)
Adapter proteins p-KIT complexComplexREACT_111421 (Reactome)
Adapter proteinsProteinREACT_111747 (Reactome)
CBL

Grb2/p-APS

p-c-Kit complex
ComplexREACT_111310 (Reactome)
CBL ProteinP22681 (Uniprot-TrEMBL)
CBLProteinP22681 (Uniprot-TrEMBL)
CHEK1 ProteinO14757 (Uniprot-TrEMBL)
Endopeptidases for SCF processingProteinREACT_111360 (Reactome)
FER ProteinP16591 (Uniprot-TrEMBL)
FES ProteinP07332 (Uniprot-TrEMBL)
FYNProteinP06241 (Uniprot-TrEMBL)
GAB2

GRB2 p-SHP2

p-KIT complex
ComplexREACT_111599 (Reactome)
GAB2 ProteinQ9UQC2 (Uniprot-TrEMBL)
GAB2ProteinQ9UQC2 (Uniprot-TrEMBL)
GDP MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GRAP ProteinQ13588 (Uniprot-TrEMBL)
GRAP2 ProteinO75791 (Uniprot-TrEMBL)
GRB10 ProteinQ13322 (Uniprot-TrEMBL)
GRB2

SOS1

p-KIT complex
ComplexREACT_111435 (Reactome)
GRB2 SOS1ComplexREACT_4435 (Reactome)
GRB2

p-SHP2

p-KIT complex
ComplexREACT_111665 (Reactome)
GRB2-1 Protein