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Review
. 2014 Jun 30:5:181.
doi: 10.3389/fgene.2014.00181. eCollection 2014.

Phosphorylation of unique domains of Src family kinases

Irene Amata  1 , Mariano Maffei  1 , Miquel Pons  1
Affiliations
Review

Phosphorylation of unique domains of Src family kinases

Irene Amata et al. Front Genet. .

Abstract

Members of the Src family of kinases (SFKs) are non-receptor tyrosine kinases involved in numerous signal transduction pathways. The catalytic, SH3 and SH2 domains are attached to the membrane-anchoring SH4 domain through the intrinsically disordered "Unique" domains, which exhibit strong sequence divergence among SFK members. In the last decade, structural and biochemical studies have begun to uncover the crucial role of the Unique domain in the regulation of SFK activity. This mini-review discusses what is known about the phosphorylation events taking place on the SFK Unique domains, and their biological relevance. The modulation by phosphorylation of biologically relevant inter- and intra- molecular interactions of Src, as well as the existence of complex phosphorylation/dephosphorylation patterns observed for the Unique domain of Src, reinforces the important functional role of the Unique domain in the regulation mechanisms of the Src kinases and, in a wider context, of intrinsically disordered regions in cellular processes.

Keywords: IDPs; IDRs; SFKs; Src; phosphorylation; unique domain.

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Figures

FIGURE 1
FIGURE 1
Phosphorylation and lipid binding sites in the Unique domain of SFK. Alignment of the UD sequences of the ten SFK. The alignment has been manually edited to emphasize the similarities in regions that are known to be functionally relevant in at least one SFK member. Residues highlighted in green are identified as phosphorylation sites in PhosphoSitePlus (Hornbeck et al., 2012). Conservation of phosphorylation sites was used as a reference in the alignment presented.
FIGURE 2
FIGURE 2
Phosphorylation sites in the UD of Src and their relationship with the two lipid-binding regions: the classical SH4 domain and the ULBR.
See this image and copyright information in PMC

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