PMID- 10445857
OWN - NLM
STAT- MEDLINE
DCOM- 19990907
LR  - 20211203
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 26
DP  - 1999 Jul 1
TI  - Biological and biochemical properties of Ret with kinase domain mutations 
      identified in multiple endocrine neoplasia type 2B and familial medullary thyroid 
      carcinoma.
PG  - 3919-22
AB  - Several mutations were identified in the kinase domain of the RET proto-oncogene 
      in patients with multiple endocrine neoplasia (MEN) 2B, familial medullary 
      thyroid carcinoma (FMTC) or sporadic medullary thyroid carcinoma. We introduced 
      seven mutations (glutamic acid 768-->aspartic acid (E768D), valine 804-->leucine 
      (V804L), alanine 883-->phenylalanine (A883F), serine 891-->alanine (S891A), 
      methionine 918-->threonine (M918T), alanine 919-->proline (A919P) and 
      E768D/A919P) into the short and long isoforms of RET cDNA and transfected the 
      mutant cDNAs into NIH3T3 cells. The transforming activity of the long isoform of 
      Ret with each mutation was much higher that that of its short isoform. Based on 
      the levels of the transforming activity, these mutant RET genes were classified 
      into two groups; a group with high transforming activity (A883F, M918T and 
      E768D/A919P) and a group with low transforming activity (E768D, V804L, S891A and 
      A919P) (designated high group and low group). Interestingly, the level of 
      transforming activity correlated with clinical phenotypes; high group Ret with 
      the A883F or M918T mutation and low group Ret with the E768D, V804L or S891A 
      mutation were associated with the development of MEN 2B and FMTC, respectively. 
      In addition, we found that substitution of phenylalanine for tyrosine 905 present 
      in the kinase domain abolished both transforming and autophosphorylation 
      activities of low group Ret whereas it did not affect the activities of high 
      group Ret.
FAU - Iwashita, T
AU  - Iwashita T
AD  - Department of Pathology, Nagoya University School of Medicine, Japan.
FAU - Kato, M
AU  - Kato M
FAU - Murakami, H
AU  - Murakami H
FAU - Asai, N
AU  - Asai N
FAU - Ishiguro, Y
AU  - Ishiguro Y
FAU - Ito, S
AU  - Ito S
FAU - Iwata, Y
AU  - Iwata Y
FAU - Kawai, K
AU  - Kawai K
FAU - Asai, M
AU  - Asai M
FAU - Kurokawa, K
AU  - Kurokawa K
FAU - Kajita, H
AU  - Kajita H
FAU - Takahashi, M
AU  - Takahashi M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Drosophila Proteins)
RN  - 0 (MAS1 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Mas)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-ret)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Ret protein, Drosophila)
RN  - EC 2.7.10.2 (src-Family Kinases)
SB  - IM
MH  - Amino Acid Substitution
MH  - Carcinoma, Medullary/enzymology/*genetics
MH  - Cell Transformation, Neoplastic/genetics
MH  - *Drosophila Proteins
MH  - Female
MH  - Humans
MH  - Japan
MH  - Male
MH  - Multiple Endocrine Neoplasia Type 2b/enzymology/*genetics
MH  - Mutagenesis, Site-Directed
MH  - Neoplasm Proteins/genetics/*physiology
MH  - Neoplastic Syndromes, Hereditary/*genetics
MH  - Oncogenes
MH  - Proto-Oncogene Mas
MH  - Proto-Oncogene Proteins/chemistry/genetics/*physiology
MH  - Proto-Oncogene Proteins c-ret
MH  - Receptor Protein-Tyrosine Kinases/chemistry/genetics/*physiology
MH  - Structure-Activity Relationship
MH  - Thyroid Neoplasms/enzymology/*genetics
MH  - src-Family Kinases/*genetics
EDAT- 1999/08/13 00:00
MHDA- 1999/08/13 00:01
CRDT- 1999/08/13 00:00
PHST- 1999/08/13 00:00 [pubmed]
PHST- 1999/08/13 00:01 [medline]
PHST- 1999/08/13 00:00 [entrez]
AID - 10.1038/sj.onc.1202742 [doi]
PST - ppublish
SO  - Oncogene. 1999 Jul 1;18(26):3919-22. doi: 10.1038/sj.onc.1202742.