Akira Imamoto, D.D.S., Ph.D.

APPOINTMENTS

  • Associate Professor, The Ben May Department for Cancer Research, UCCCC, Department of Molecular Oncology, Committee on Cancer Biology, Committee on Cellular and Molecular Physiology, Committee on Developmental Biology

EDUCATION

Ph.D., Osaka University, 1988

D.D.S., Osaka University School of 
     Dentistry, 1984

CONTACT INFORMATION

The University of Chicago
GCIS W332
929 East 57th Street
Chicago, Illinois 60637

aimamoto@uchicago.edu

Phone:  (773) 834-1258

RESEARCH SUMMARY

Tyrosine Kinase-mediated Signaling to the Cytoskeleton in Mouse Development and in Cancer.

Our laboratory is currently focusing on the elucidation of the mechanism by which tyrosine kinases mediate signals to the cytoskeleton during mouse development as well as in cancer using gene targeting technology and mouse genetics. We are also investigating the connection between tyrosine kinases and human malignancies at the interface of the cytoskeleton.

Like other abnormal genes that are linked to cancer, the oncogene v-src has multiple effects on mammalian cells, including, most dramatically, the induction of cellular transformation, which is believed to correspond to the change of normal cells to cancer. v-src was identified as the first oncogene encoding a protein tyrosine kinase (PTK), an enzyme that transfers a phosphoryl group in an energy-dependent manner onto a tyrosine residue of a protein (known as tyrosine phosphorylation) to modify the function of the target. Most cancer cells have elevated levels of tyrosine kinase activity. Unlike its normal cellular counterpart (c-src) from which the oncogene is derived, the product of v-src lacks a key regulatory tyrosine residue, which when phosphorylated represses tyrosine kinase activity. Therefore, the v-Src protein lacks this regulatory mechanism and is always active. Another class of PTKs, Csk and Ctk, phosphorylate in vitro the regulatory tyrosine conserved within the Src family. By phosphorylation at the key tyrosine residue, these PTKs regulate cellular Src, which otherwise is potentially oncogenic.

Knock-out (genetic inactivation) of the csk gene in the mouse resulted in embryonic lethality with lack of: i) cephalic neural tube closure, ii) inversion of the germ layers, and iii) connection of the allantois to the chorion; indicating that regulation Src family PTKs by Csk is essential during mouse development. Further analysis of cells isolated from mutant embryos suggested that the phenotype of csk homozygous mutants may result from rearrangement of the cytoskeleton. Interestingly, one of the cytoskeletal proteins hyperphosphorylated in csk mutant cells is also known to be amplified in a population of breast cancers with poor prognosis. Thus, cytoskeletal proteins may play a role in malignant progression of cancer cells.

Research Papers in PubMed