PMID- 10523834
OWN - NLM
STAT- MEDLINE
DCOM- 19991105
LR  - 20101118
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 40
DP  - 1999 Sep 30
TI  - Isoforms of c-KIT differ in activation of signalling pathways and transformation 
      of NIH3T3 fibroblasts.
PG  - 5573-81
AB  - Alternate splicing of mRNA encoding c-KIT results in isoforms which differ in the
      presence or absence of four amino acids (GNNK) in the juxtamembrane region of the
      extracellular domain of the receptor. In this study we show that these isoforms
      of human c-KIT, expressed at similar levels in NIH3T3 cells, display differential
      effects on various attributes of transformation. The GNNK- isoform strongly
      promoted anchorage independent growth (colony formation in semi-solid medium),
      loss of contact inhibition (focus formation), and led to tumorigenicity in nude
      mice. In contrast, the GNNK+ isoform elicited colony formation but relatively
      poor focus formation and no tumorigenicity. Saturation binding analysis indicated
      that the isoforms do not differ significantly in their affinity for the KIT
      ligand, Steel Factor (SLF). Negligible ligand-independent receptor
      phosphorylation was observed in either case but, after ligand stimulation, the
      GNNK- isoform displayed more rapid and extensive tyrosine autophosphorylation and
      faster internalization. Both isoforms recruited the p85 subunit of
      phosphatidylinositol 3-kinase and led to similar phosphorylation of its
      downstream effector c-Akt, but the GNNK- isoform gave rise to more MAP kinase
      phosphorylation. Thus the c-KIT isoforms display different signalling
      characteristics and have different transforming activity in NIH3T3 cells.
FAU - Caruana, G
AU  - Caruana G
AD  - Division of Haematology, Hanson Centre for Cancer Research, Institute of Medical 
      and Veterinary Science, Adelaide, SA 5000, Australia.
FAU - Cambareri, A C
AU  - Cambareri AC
FAU - Ashman, L K
AU  - Ashman LK
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (DNA, Complementary)
RN  - 0 (Protein Isoforms)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Stem Cell Factor)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
SB  - IM
MH  - 3T3 Cells/pathology/transplantation
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Adhesion
MH  - Cell Transformation, Neoplastic/*metabolism
MH  - DNA, Complementary/genetics
MH  - Humans
MH  - Mice
MH  - Mice, Nude
MH  - Phosphatidylinositol 3-Kinases/physiology
MH  - Protein Isoforms/genetics/*physiology
MH  - Proto-Oncogene Proteins c-kit/*physiology
MH  - *RNA Splicing
MH  - Recombinant Fusion Proteins/genetics/physiology
MH  - Signal Transduction/*physiology
MH  - Stem Cell Factor/physiology
MH  - Transfection
MH  - Tumor Stem Cell Assay
EDAT- 1999/10/19 00:00
MHDA- 1999/10/19 00:01
CRDT- 1999/10/19 00:00
PHST- 1999/10/19 00:00 [pubmed]
PHST- 1999/10/19 00:01 [medline]
PHST- 1999/10/19 00:00 [entrez]
AID - 10.1038/sj.onc.1202939 [doi]
PST - ppublish
SO  - Oncogene. 1999 Sep 30;18(40):5573-81. doi: 10.1038/sj.onc.1202939.