Tyrosine Kinases

Receptor Linked

Non-Receptor Linked

Overview

Protein Kinase Tables Home

Tyrosine Kinases — Receptor Linked

Abbreviations

Currently
Accepted
Name

EGFR
(E 3641 (human),
E 2645 (human))

HER-2/Neu/cerbB2

PDGFR

IGF1-R

FGFR
(F 2897)

Ligands

EGF
(E 9644 (human),
E 4127 (m))
TGF (T 7924 (human),
T 9533 (r))
Amphiregulin
(A 7080 (human))

Unknown

PDGF
(P 3201 (BB) (human),
P 3076 (AA) (human))

IGF-1
(I 3769 (human))

FGF
(F 3133 (bovine),
F 5542 (a) (human),
F 0291 (b) (human))

Structural
Information

1210 aa (human)

1255 aa (human)

1098 (human)
1106 (human)

1367 aa (human)

822 aa (mouse)

Mechanism
of Activation

Ligand-induced dimerization
followed by
trans-auto-
phosphorylation

Probably by hetero-
dimerization

Dimerization of
the receptor
followed by
trans-auto-
phosphorylation

Trans-auto-
phosphorylation
within the dimer

Dimerization of
the receptor
followed by
trans-auto-
phosphorylation

Selective
Inhibitors

AG 1478
(T 4182)
PD 153,035

AG 825
AG 879
(T 2067)

AG 1295
(T 3932)
AG 1296
(T 4057)
AGL 2043

AG 1024
AG 538

SU 5402

Non-Selective
Inhibitors

DAPH 1
(D-210)
Lavendustin A
(L 2400)
Genistein
(G 6649,
G 6776)
Herbimycin A
(H 6649)

DAPH 1
(D-210)
Lavendustin A
(L 2400)
Genistein
(G 6649,
G 6776)
Herbimycin A
(H 6649)

Lavendustin A
(L 2400)
Genistein
(G 6649,
G 6776)
Herbimycin A
(H 6649)

Not tested

SU 4984

Diseases
Implicated

Gliomas, squamous cell carcinoma, papilloma, psoriasis

Breast and ovarian carcinomas, non-small cell lung cancer

Glioblastomas, atherosclerosis, restenosis

Prostate cancer, breast cancer

—

Radioligands
of Choice

¹²⁵I]-EGF

—

[¹²⁵I]-hPDGF

[¹²⁵I]-IGF-1

[¹²⁵I]-FGF

Abbreviations
AG 538: 3,4-Dihydroxy[ (3',4'-dihydroxy)benzoyl]-cis-cinnamonitrile
AG 825: 4-Hydroxy-3-methoxy-5-(benzothiazoylthiomethyl)benzylidenecyanoacetamide
AG 879: -Cyano-(3,5-di-t-butyl-4-hydroxy)thiocinnamide
AG 1024: 3-Bromo-5-t-butyl-4-hydroxybenzylidenemalonitrile
AG 1295: 6,7-Dimethyl-2-phenylquinoxaline
AG 1296: 6,7-Dimethoxy-2-phenylquinoxaline
AG 1478: N-(3-Chlorophenyl)-6,7-dimethoxy-4-quinazolinamine
AGL 2043: 1,2-Dimethyl-6-(2-thiophene)imidazolo[5,4-g]-quinoxaline
DAPH 1: 4,5-Dianilinophthalimide
EGF: Epidermal growth factor
FGF: Fibroblast growth factor
IGF-1: Insulin-like growth factor-1
PD 153,035: 4-(3-Bromoanilino)-6,7-dimethoxyquinazoline
PDGF: Platelet-derived growth factor
SU 5402: 3-[3-(2-Carboxyethyl)-4-methylpyrrol-2-methylidenyl]-2-indolinone
SU 4984: 3-[4-(1-Formylpiperazin-4-yl)benzylidenyl]-2-indolinone
TGF: Transforming growth factor
a: acidic
b: basic
m: mouse
r: rat

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Tyrosine Kinases — Non-Receptor Linked

Abbreviations

Currently
Accepted
Name

pp60 c-Src and src family kinases

Bcr-Abl

Jak-2 and Jak family kinases

Ligands

None

None

None

Structural
Information

542 aa (mouse)

a

1133 aa (human)

Mechanism
of Activation

Dephosphorylation of a C-terminal phosphotyrosine

Dimerization

Recruitment followed by conformational change

Selective
Inhibitors

PP1
PP2
7,8-DHIC

AG 1112
AG 957

—

Non-Selective
Inhibitors

Herbimycin A (H 6649)
AG 18
AG 34
AG 82

Herbimycin A (H 6649)

Herbimycin A (H 6649)

Diseases
Implicated

In its viral form (v-Src) cancer in chicken; activated in certain human cancers (c-Src)

Bcr-Abl causes chronic myeloid leukemia ^a

Pre-B recurrent acute lymphoblastic leukemia

Abbreviations
AG 18: -Cyano-(3,4-dihydroxy) cinnamonitrile
AG 34: 3,4-Dihydroxy-5-methoxybenzylidine malononitrile
AG 82: -Cyano-(3,4,5-trihydroxy)cinnamonitrile
AG 957: 4-Amino-N-(2,5-dihydroxybenzyl)methylbenzoate
AG 1112: 3-Indolidene malononitrile [-(3-amino-4-cyano-5-yl)]pyrazole
7,8-DHIC: 7,8-Dehydroxy-isoquinoline-3-carboxamide
PP1: 4-Amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine
PP2: 4-Amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine

Footnotes

a Bcr-Abl is a chimeric protein consisting of the amino terminal 927 amino acids or the amino terminal 426 amino acids of Bcr fused to the second exon of the tyrosine kinase Abl.

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