Protein tyrosine phosphatase α (PTPα) is believed to dephosphorylate physiologically the Src protooncogene at phosphotyrosine (pTyr)527, a critical negative-regulatory residue. It thereby activates Src, and PTPα overexpression neoplastically transforms NIH 3T3 cells. pTyr789 in PTPα is constitutively phosphorylated and binds Grb2, an interaction that may inhibit PTPα activity. We show here that this phosphorylation also specifically enables PTPα to dephosphorylate pTyr527. Tyr789→Phe mutation abrogates PTPα-Src binding, dephosphorylation of pTyr527 (although not of other substrates), and neoplastic transformation by overexpressed PTPα in vivo. We suggest that pTyr789 enables pTyr527 dephosphorylation by a pilot binding with the Src SH2 domain that displaces the intramolecular pTyr527-SH2 binding. Consistent with model predictions, we find that excess SH2 domains can disrupt PTPα-Src binding and can block PTPα-mediated dephosphorylation and activation in proportion to their affinity for pTyr789. Moreover, we show that, as predicted by the model, catalytically defective PTPα has reduced Src binding in vivo. The displacement mechanism provides another potential control point for physiological regulation of Src-family signal transduction pathways.

Epigenetic mechanisms are crucial mediators of appropriate plant reactions to adverse environments, but their involvement in long-term adaptation is less clear. Here, we established two rice epimutation accumulation lines by applying drought conditions to 11 successive generations of two rice varieties. We took advantage of recent technical advances to examine the role of DNA methylation variations on rice adaptation to drought stress. We found that multi-generational drought improved the drought adaptability of offspring in upland fields. At single-base resolution, we discovered non-random appearance of drought-induced epimutations. Moreover, we found that a high proportion of drought-induced epimutations maintained their altered DNA methylation status in advanced generations. In addition, genes related to transgenerational epimutations directly participated in stress-responsive pathways. Analysis based on a cluster of drought-responsive genes revealed that their DNA methylation patterns were affected by multi-generational drought. These results suggested that epigenetic mechanisms play important roles in rice adaptations to upland growth conditions. Epigenetic variations have morphological, physiological and ecological consequences and are heritable across generations, suggesting that epigenetics can be considered an important regulatory mechanism in plant long-term adaptation and evolution under adverse environments.

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