![]() Internal receptors, also known as intracellular or cytoplasmic receptors, are found in the cytoplasm of the cell and respond to hydrophobic ligand molecules that are able to travel across the plasma membrane. There are two types of receptors, internal receptors and cell-surface receptors. cytoplasmic (initiation factors of translation, apoptosismachinery, oestrogenrec.Receptors are protein molecules in the target cell or on its surface that bind ligand.Parallel MAPK pathways ERK pathway p38 pathway JNK pathway Ligands and activators Mitogens Stress/Cytokines MEKK1, DLK, MLK2, ASK, TAK1, TAO, TAO2 MAPKKK A-raf, B-raf, C-raf MAPKK MEK1, MEK2 MEK3, MEK6 MEK4, MEK7 PDK1 MAPK ERK1, ERK2, ERK5 ERK3, ERK4 p38a, b, d JNK1, 2, 3 RSK1 RSK2 RSK3 RSK4 MSK1 MSK2 MNK1 MK2 MK3 MK5B MK MNK2 Ras-MAPK pathway Growthfactor/Hormone Receptor PTK Plasmamembrane RAS Active RAS Cytoplasm RAF ? SOS GDP P P P P P P P P GTP GRB2 Guanine nucleotide exchange factor (GEF) MEK1 MEK1 P P P P P P P P Adaptor ERK2 ERK2 ERK2 ERK2 + Elk-1 Elk-1 Nucleus Genetranscription SRE Elk-1 cFos SRF AP-1 Members of thesignalingcomplex Growthfactor/Hormone Receptor PTK Plasma membrane Cytoplasm PI3K SHC GRB2 SOS RAS MEK Y Y Y Y SRC PKC RAF MAPKs Y Y RSK PLCg FAK Transcriptionalregulation Differentiation Differentiation/Growth Nucleus Src/Syk family kinases, SHP-1, PLCg, Sos, Vav, RasGAP, STAT1 etc.4Signal complex (adapter proteins, kinases etc.)ĭimerization of GF receptors Dimerization Plasmamembrane Cytoplasm ATP ATP P P P P P P P P P P Juxtamembraneregion Activation and catalyticloop (substrateprecluding) C-terminalregion Activation and catalytic loop (substrate accessible)Īutophosphorylation of RTKs P P PDGFR EGFR P P P P Phosphotyrosine Y559 Y581 Y716 Y741 Y751 Y771 Y1009 Y1021 Phosphotyrosine Y992 Y1045 Y1068 Y1086 Y1148 Y1173 P P P P P P P P P P P P P P P P P P Shc PI3K Cbl SLP76 GRB2 Crk SHP-1 SRC IRS-1 Abl Nck STAT1 PLCg p120 Ras-Gap.Receptor tyrosinekinasefamily Ltk Alk FGFR1 FGFR2 FGFR3 FGFR4 PDGFR PDGFRβ CSF1R Kit Kit2 VEGFR1 VEGFR2 VEGFR3 Met Ron Sea TrkA TrkB TrkC Tie Tie2 Ret EGFR ErbB2 ErbB3 ErbB4 INSR IGF1R IRR Eph Eck Eek Erk Elk Ehk1 Ehk2 Sek Hek Hek11 Cek-9 Myk-1 Myk-2 Ryk Ros Ror1 Ror2 Torpedo Torso Axl Mer Sky DDR EGF-like Factor VIII-like C1r-like Cysteine-rich Fibronectin III Kinase Kringle Glicyne-rich Cadherin IG-like Leucine-rich Acid-box ![]() ![]()
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