RTK

RTK

RTK

RTK

RTK

RTK

RTK

RTK

PDGF RTK

RTK

RTK

RTK

PDGF

RTK

EGF

EGF

RTK

RTK

PDGF

pp.

Kit

RTK

RTK

RTK

PDGF

KitSCF

Kit

SCF

Structural biology of receptor tyrosine kinase KitSatoru Yuzawa and Joseph SchlessingerYale UniversitySchool of Medicine, Cedar Street, New Haven, CT, U.S.A.

Kit

Kit

PDGF

PDGF RTK

RTK

NRTK RTK

RTK

PDGF III

RTKKitc-kitSCFCDCSF

colony-stimulating factorM-CSFc-fms

FltFms-like tyrosine kinase PDGFPDGFRPDGFR RTK RTK

Ig

JMRjaxstamembrane region

KIDkinase insertion domain

PDGF

SCFstem cell factor

RTK RTKEGFPDGFFGFVEGFIgLCRFnKIDkinase insertion domain

CSF FltLFltligand

small helical cytokine foldCSF

SCF FltL

SCF KitCSF CSF

FltL Flt

PDGFR

PDGF cytokine knot foldPDGF

ABC D

PDGF-AA-BB-CC-DDAB

PDGF

PDGFR PDGFR-PDGFR PDGFR-PDGFR PDGFR-PDGFRPDGF

RTK

RTK

SHSrc homology PTBphospho-

tyrosine bindingRTK

RTK

RTK

ligand-mediated

hGH-hGH EPO

erythropoietin-EPO

hGH EPO

Flt-VEGFR-

IgD

VEGF

VEGFR-

VEGFVEGF VEGFR-

VEGFVEGFR-

RTK

PDGF

VEGF Ig

D-D-D

D

PDGF VEGF

cytokine knot fold

PDGFVEGF

NGFnerve growth

factor-TrkA

PDGFPDGF SCFstem cell factorCSFcol-ony stimulating factorFltLFms-like tyrosine kinaseligandPDGF-BBplatelet-derived growth factor PDBEXZSCFHMCCSFETEFltLPDGPDGF-BB

Kit

PDGF Kit

GISTmas-

tocytosisAML

SCF Kit

D-D-D-D-D

Kit

D-D-D SCF

SCF-Kit

SCF SCF-Kit

Kit

SCFKit

IgD-D-D Ig

D-D

D-D-D

D-D

Kit D-D-D

SCF

Kit D-D-D

SCF

Kit D-D-D

SCF

SCF-Kit D-D-D

VEGF-VEGF D

Kit D-D-D

Tie

SCF-Kit

SCF KitSCFstem cell factor KitKit SCF IgDDD SCF SCF IgDDSCF PDBECKitEWSCF-Kit

D BCSCF

D N

SCF D C-SCF

SCF-Kit

SCF-Kit

D D

DD

SCF-Kit SCF-SCF

SCF-KitSCF-KitSCF KitD D SCFD SCF Kit

SCF-KitSCF-Kit IgDD E F

D

PDGF

FltD

Kit PDGF

IgD

D

Kit PDGF

D

VEGF Ig

DPDGF D

VEGF VEGF

VEGF-VEGF

D

PDGF

Ig

VEGF Ig

PDGF

VEGF RTK

PDGF VEGF

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D

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DDDD Kit D E FPDGFFlt VEGF Ig

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GISTmastocytosis

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SCF Kit SCFa SCF-Kitb Kit DD DDD CSCF-KitDD DD

Ig

FGF Ig

FGF

FGF-

FGF

D

NRTK JAKJanus

kinase

JAK

gp

Fngp

IL- IL- IL- IL-

Fn

D

Kit

JMR N-

C-

N-ATP

ATPC-

ATP

A-activation segmentloop

A-

A-

A-

A-

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PDGF JMR

Eph

JMR

PDGF

ATP

RTK

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A-

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A-

JMR

A-

JMR

JMR

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A-

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PDGF

JMR

JMR

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Kit A-

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KitKitab N- C-JMRjaxtamembrane regionA-KIDkinase insertion domainADPJMRTyr Tyr A-JMR A-N- C-JMRTyr TyrA-JMRpTyr pTyr PDBPKGT

JMR

JMR

RTK

KitPDGF

Kit

JMR

PDGF

VEGF RTK

RTK

D D

RTKD-D

D-D

RTK

Kit

Yarden Opatowsky

Zhongtao ZhangValsan Mandiyan Irit Lax

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