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Evolution of Shc functions from nematode to human.
L Luzi1, S Confalonieri, P P Di Fiore
1Department of Experimental Oncology, Istituto Europeo di Oncologia, Via Ripamonti 435, 20141 Milan, Italy.
Current Opinion in Genetics & Development
|November 23, 2000
Summary
The Shc protein family evolved from one gene in fruit flies to multiple genes in mammals, creating diverse protein functions. These Shc proteins regulate crucial cellular processes like growth and apoptosis, with Ras activation being a recent evolutionary development.
Area of Science:
- Molecular Biology
- Evolutionary Biology
- Cellular Signaling
Background:
- The Shc protein family possesses a conserved modular structure: (CH2)-PTB-CH1-SH2.
- Evolution has led to increased complexity, with one Shc locus in Drosophila (dShc) expanding to at least three loci (shc, rai, sli) in mammals.
Purpose of the Study:
- To investigate the evolutionary diversification of Shc protein functions.
- To understand how alternative splicing and initiation codon usage contribute to Shc protein complexity in mammals.
Main Methods:
- Comparative analysis of Shc-like genes and proteins across species.
- Examination of sequence similarities and structure-function relationships.
- Review of genetic and biological evidence for Shc isoform functions.
Main Results:
- Mammalian genomes encode at least six Shc-like proteins from three loci due to alternative initiation and splicing.
- Mammalian Shc isoforms (p52/p46Shc, p66Shc) are implicated in diverse functions including cell growth, apoptosis, and lifespan regulation.
- Ras activation, a key Shc function, appears to be a recent evolutionary acquisition.
Conclusions:
- The Shc protein family has undergone significant functional diversification throughout evolution.
- Alternative molecular mechanisms contribute to the complexity and varied roles of Shc proteins in mammals.
- Understanding Shc evolution provides insights into cellular signaling pathways and their regulation.