Unknown

Dataset Information

0

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 (p130CAS) in the presence of activated SRC. These results demonstrate an ancient origin of the CRK/CRKL SH2-target recognition specificity. Although BCAR1 orthologs exist only in metazoans as identified by an N-terminal SH3 domain, YxxP motifs, and a C-terminal FAT-like domain, some pre-metazoan transmembrane proteins include several YxxP repeats in their cytosolic region, suggesting that they are remotely related to the BCAR1 substrate domain. Since the tyrosine kinase SRC also has a pre-metazoan origin, co-option of BCAR1-related sequences may have rewired the crka-dependent network to mediate adhesion signals in the metazoan ancestor.

SUBMITTER: Shigeno-Nakazawa Y 

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

REPOSITORIES: biostudies-literature

altmetric image

Publications


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 t  ...[more]

Similar Datasets

| S-EPMC2637924 | biostudies-literature
| S-EPMC10504328 | biostudies-literature
| S-EPMC9691542 | biostudies-literature
| S-EPMC4438107 | biostudies-literature
| S-EPMC2329691 | biostudies-literature
| S-EPMC9810535 | biostudies-literature
| S-EPMC7298416 | biostudies-literature
| S-EPMC8423806 | biostudies-literature
| S-EPMC7450096 | biostudies-literature
| S-EPMC2978717 | biostudies-literature