Transforming growth factor-β-inducible early response gene 1 is a novel substrate for atypical protein kinase Cs.
The protein kinase C (PKC) family of serine/threonine kinases consists of ten different isoforms grouped into three subfamilies, denoted classical, novel and atypical PKCs (aPKCs). The aPKCs, PKCι/λ and PKCζ serve important roles during development and in processes subverted in cancer such as cell and tissue polarity, cell proliferation, differentiation and apoptosis. In an effort to identify novel interaction partners for aPKCs, we performed a yeast two-hybrid screen with the regulatory domain of PKCι/λ as bait and identified the Krüppel-like factors family protein TIEG1 as a putative interaction partner for PKCι/λ. We confirmed the interaction of both aPKCs with TIEG1 in vitro and in cells, and found that both aPKCs phosphorylate the DNA-binding domain of TIEG1 on two critical residues. Interestingly, the aPKC-mediated phosphorylation of TIEG1 affected its DNA-binding activity, subnuclear localization and transactivation potential.
Alemu
Endalkachew A
EA
Molecular Cancer Research Group, Institute of Medical Biology, University of Tromsö, Tromsö 9037, Norway.
Sjøttem
Eva
E
Outzen
Heidi
H
Larsen
Kenneth B
KB
Holm
Turid
T
Bjørkøy
Geir
G
Johansen
Terje
T
D000595:Amino Acid Sequence; D051765:Early Growth Response Transcription Factors / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism*; D016415:Sequence Alignment; D020798:Two-Hybrid System Techniques
D051765:Early Growth Response Transcription Factors; C098111:KLF10 protein, human; D051741:Kruppel-Like Transcription Factors; D011493:Protein Kinase C