A pre-metazoan origin of the CRK gene family and co-opted signaling network.

ABSTRACT: CRK and CRKL adapter proteins play essential roles in development and cancer through their SRC homology 2 and 3 (SH2 and SH3) domains. To gain insight into the origin of their shared functions, we have investigated their evolutionary history. We propose a term, crk/crkl ancestral (crka), for orthologs in invertebrates before the divergence of CRK and CRKL in the vertebrate ancestor. We have isolated two orthologs expressed in the choanoflagellate Monosiga brevicollis, a unicellular relative to the metazoans. Consistent with its highly-conserved three-dimensional structure, the SH2 domain of M. brevicollis crka1 can bind to the mammalian CRK/CRKL SH2 binding consensus phospho-YxxP, and to the SRC substrate/focal adhesion protein BCAR1 (p130^CAS) in the presence of activated SRC. T

SUBMITTER: Shigeno-Nakazawa Y 

PROVIDER: S-EPMC5043372 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature