Emerging role of tyrosine phosphatase, TCPTP, in the organelles of the early secretory pathway

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• 作者：Madhavi Muppirala ; Vijay Gupta¹ ; Ghanshyam Swarup ; ^{gshyam@ccmb.res.in}
• 关键词：CD ; Crohn's disease ; ER ; endoplasmic reticulum ; ERGIC ; ER&ndash ; Golgi intermediate compartment ; IEC ; intestinal epithelial cells ; SNARE ; soluble N-ethylmaleimide-sensitive factor attachment protein receptor ; NLS ; nuclear localization signal ; PTK ; protein
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Cell Research
• 出版年：2013
• 出版时间：May, 2013
• 年：2013
• 卷：1833
• 期：5
• 页码：1125-1132
• 全文大小：852 K

文摘

T-cell protein tyrosine phosphatase, TCPTP, is a ubiquitously expressed non-receptor type tyrosine phosphatase. There are two splice variants of TCPTP, TC48 and TC45, which differ in their sub-cellular localizations and functions. TC45 is a nuclear protein, which has both nuclear and cytoplasmic substrates, and is involved in many signaling events including endocytic recycling of platelet-derived growth factor ¦Â-receptor. TC48 is a predominantly endoplasmic reticulum (ER)-localizing protein, which dephosphorylates some of the substrates of TC45 at the ER. However, recently few specific substrates for TC48 have been identified. These include C3G (RapGEF1), syntaxin 17 and BCR-Abl. TC48 moves from the ER to post-ER compartments, the ER-Golgi intermediate compartment (ERGIC) and Golgi, and it is retrieved back to the ER. The retrieval of ER proteins from post-ER compartments is generally believed as a mechanism of targeting these proteins to the ER. However, it is possible that this shuttling of TC48 serves to regulate signaling in the early secretory pathway. For example, TC48 dephosphorylates phosphorylated C3G at the Golgi and inhibits neurite outgrowth. TC48 interacts with and dephosphorylates syntaxin 17, which is an ER and ERGIC-localizing protein involved in vesicle transport. A yeast two-hybrid screen identified several unique interacting partners of TC48 belonging to two groups ¡ª proteins involved in vesicle trafficking and proteins involved in cell adhesion. These interacting proteins could be substrates or regulators of TC48 function and localization. Thus, the role of TC48 seems to be more diverse, which is still to be explored.