Cutting Edge: Recruitment of the Ancestral fyn Gene During Emergence of the Adaptive Immune System1

The adaptive immune system (AIS) is characterized by the MHC molecules and the rearranging Ag receptors, and was established in a common ancestor of jawed vertebrates. Fyn, a Src-family tyrosine kinases, is important for normal development and function of T lymphocytes and neuronal cells. Indeed, as the result of an alternative splicing of a distinct exon 7, fyn encodes for two isoforms, FynT in T lymphocytes and FynB in the brain. How this alternative splicing of fyn transcripts has emerged and evolved in relation to the setting of the AIS remains to be established. In this study, we show that exon capture in a vertebrate ancestor by the fynT-like gene has yielded a novel fyn-encoded isoform, fynB. Unexpectedly, the newly established AIS recruited the ancestral Fyn isoform, FynT, whereas the CNS expresses the most recent one, FynB. These results shed new light on the emergence of the AIS.

[1]  J. Laplanche,et al.  Signal transduction through prion protein. , 2000, Science.

[2]  A. Israël,et al.  Altered Expression of Tyrosine Kinases of the Src and Syk Families in Human T-Cell Leukemia Virus Type 1-Infected T-Cell Lines , 1999, Journal of Virology.

[3]  D. Sanchez,et al.  Generation of evolutionary novelty by functional shift. , 1999, BioEssays : news and reviews in molecular, cellular and developmental biology.

[4]  John Kuriyan,et al.  Intramolecular Regulatory Interactions in the Src Family Kinase Hck Probed by Mutagenesis of a Conserved Tryptophan Residue* , 1998, The Journal of Biological Chemistry.

[5]  Giulio Superti‐Furga,et al.  The role of the linker between the SH2 domain and catalytic domain in the regulation and function of Src , 1997, The EMBO journal.

[6]  J. Kuriyan,et al.  Structures of Src-family tyrosine kinases. , 1997, Current opinion in structural biology.

[7]  Michael J. Eck,et al.  Three-dimensional structure of the tyrosine kinase c-Src , 1997, Nature.

[8]  J. Thompson,et al.  CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. , 1994, Nucleic acids research.

[9]  I. Weissman,et al.  Molecular evolution of the vertebrate immune system. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[10]  M. Fournel,et al.  Oncogenic activation of p59fyn tyrosine protein kinase by mutation of its carboxyl-terminal site of tyrosine phosphorylation, tyrosine 528. , 1994, The Journal of biological chemistry.

[11]  Sudhir Kumar,et al.  MEGA: Molecular Evolutionary Genetics Analysis software for microcomputers , 1994, Comput. Appl. Biosci..

[12]  E. Kandel,et al.  Impaired long-term potentiation, spatial learning, and hippocampal development in fyn mutant mice. , 1992, Science.

[13]  R. Perlmutter,et al.  Defective T cell receptor signaling in mice lacking the thymic isoform of p59 fyn , 1992, Cell.

[14]  Cook Mp,et al.  Expression of a novel form of the fyn proto-oncogene in hematopoietic cells. , 1989 .

[15]  A. Hughes Evolution of the src-related protein tyrosine kinases. , 1996, Journal of molecular evolution.

[16]  L. Du Pasquier Origin and evolution of the vertebrate immune system. , 1992, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[17]  R. Perlmutter,et al.  Expression of a novel form of the fyn proto-oncogene in hematopoietic cells. , 1989, The New biologist.