Research

Regulation of Anchorage Signals Through Shc

Specialized metazoan cells have diverse functions which require them to interact differently with the body’s matrix scaffolds. Resident tissue cells, for instance, have strong anchorage capabilities and requirements that maintain tissue organization and structure, whereas blood cells need to release into a liquid environment to function properly.

Such differences in matrix adhesion are reflected in prominent shape differences, which in turn are controlled by small GTPases of the Rho and Ras families. These molecular switches coordinate cell fate signals with cytoskeletal dynamics, and are thus of major importance in understanding anchorage biology.

The SHC1 gene expresses proteins that regulate and counter-regulate Rho and Ras signals in response to adhesion status, and its isoforms toggle GTPase biasing towards or away from anchorage independence.

The two chief isoforms of Shc are p52Shc and p66Shc, which operate from integrin structures and differentially recruit Rho or Ras GTPase activators, or GEFs, in response to mechanical tension.

Ongoing projects in the lab are focused on in vitro and in vivo models of exploring the molecular basis for translating mechanical signals generated by matrix adhesion to proliferative, cytoskeletal, or death signals.