Songyang Z, Shoelson S E, Chaudhuri M, Gish G, Pawson T, Haser W G, King F, Roberts T, Ratnofsky S, Lechleider R J
Cellular and Molecular Physiology Harvard Medical School, Beth Israel Hospital, Boston, Massachusetts 02115.
Cell. 1993 Mar 12;72(5):767-78. doi: 10.1016/0092-8674(93)90404-e.
A phosphopeptide library was used to determine the sequence specificity of the peptide-binding sites of SH2 domains. One group of SH2 domains (Src, Fyn, Lck, Fgr, Abl, Crk, and Nck) preferred sequences with the general motif pTyr-hydrophilic-hydrophilic-Ile/Pro while another group (SH2 domains of p85, phospholipase C-gamma, and SHPTP2) selected the general motif pTyr-hydrophobic-X-hydrophobic. Individual members of these groups selected unique sequences, except the Src subfamily (Src, Fyn, Lck, and Fgr), which all selected the sequence pTyr-Glu-Glu-Ile. The variability in SH2 domain sequences at likely sites of contact provides a structural basis for the phosphopeptide selectivity of these families. Possible in vivo binding sites of the SH2 domains are discussed.
利用一个磷酸化肽文库来确定SH2结构域的肽结合位点的序列特异性。一组SH2结构域（Src、Fyn、Lck、Fgr、Abl、Crk和Nck）偏好具有pTyr-亲水-亲水-Ile/Pro一般基序的序列，而另一组（p85的SH2结构域、磷脂酶C-γ和SHPTP2）选择pTyr-疏水-X-疏水的一般基序。这些组中的个别成员选择了独特的序列，但Src亚家族（Src、Fyn、Lck和Fgr）除外，它们都选择了pTyr-Glu-Glu-Ile序列。SH2结构域在可能的接触位点的序列变异性为这些家族的磷酸化肽选择性提供了结构基础。文中还讨论了SH2结构域在体内可能的结合位点。
