Ser194

Site Information
LAKAQETsGEEIsKF SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 451660

In vivo Characterization
Methods used to characterize site in vivo:	2D analysis ( 14 ) , [32P] bio-synthetic labeling ( 20 , 21 ) , electrophoretic mobility shift ( 19 ) , immunoprecipitation ( 1 , 2 , 16 , 21 ) , mass spectrometry ( 1 , 2 , 5 , 6 , 7 , 8 , 11 , 12 , 13 , 15 , 16 , 17 , 18 , 19 ) , multiple reaction monitoring (MRM) ( 3 ) , mutation of modification site ( 14 ) , peptide sequencing ( 20 , 21 ) , phospho-antibody ( 2 , 3 , 4 , 5 , 7 , 8 , 9 , 10 , 14 ) , phosphoamino acid analysis ( 20 ) , western blotting ( 2 , 3 , 5 , 7 , 8 , 9 , 10 , 14 )
Disease tissue studied:	HER2 positive breast cancer ( 6 ) , luminal A breast cancer ( 6 ) , luminal B breast cancer ( 6 ) , breast cancer, triple negative ( 6 ) , liver cancer ( 2 , 7 , 8 , 9 , 10 , 19 ) , lung cancer ( 13 ) , non-small cell lung adenocarcinoma ( 13 ) , pancreatic ductal adenocarcinoma ( 12 ) , Fetal growth restriction ( 15 , 18 )
Relevant cell line - cell type - tissue:	'pancreatic, ductal'-pancreas ( 12 ) , amniotic fluid ( 15 , 16 , 17 , 18 ) , blood ( 10 ) , breast ( 6 ) , CHO (fibroblast) [EphB1 (human), transfection] ( 20 , 21 ) , CHO (fibroblast) ( 14 ) , endometrial stromal ( 1 , 3 ) , HepG2 (hepatic) ( 2 , 7 , 8 , 9 , 10 , 19 ) , liver ( 11 ) , lung ( 13 ) , stromal ( 5 )

Upstream Regulation
Regulatory protein:	DEPTOR (human) ( 9 , 10 ) , ERK1 (human) ( 9 ) , GCN2 (human) ( 9 ) , Raptor (human) ( 8 , 9 , 10 ) , RICTOR (human) ( 8 , 9 , 10 ) , TSC2 (human) ( 8 )
Putative in vivo kinases:	CK2A1 (human) ( 7 , 9 , 10 ) , PKACA (human) ( 1 ) , PKCA (human) ( 2 , 7 )
Kinases, in vitro:	CK2A1 (human) ( 7 )
Treatments:	8-Rp-cAMP ( 5 ) , amino_acid_starvation ( 19 ) , bisindolylmaleimide_II ( 2 ) , fetal growth restriction ( 10 ) , hypoxia ( 1 , 3 , 8 , 19 ) , leucine ( 9 ) , leucine_deprivation ( 2 , 5 , 7 , 9 ) , MPA ( 5 ) , phorbol_ester ( 2 ) , rapamycin ( 3 , 8 , 9 , 10 ) , siRNA ( 2 ) , TBB ( 2 , 9 ) , U0126 ( 9 )

Downstream Regulation
Effects of modification on IGFBP1:	activity, induced ( 19 ) , activity, inhibited ( 3 , 9 ) , molecular association, regulation ( 3 , 15 , 19 ) , phosphorylation ( 9 )
Effects of modification on biological processes:	signaling pathway regulation ( 3 )
Induce interaction with:	CK2B (human) ( 3 ) , IGF1 (human) ( 15 , 19 )

Disease / Diagnostics Relevance
Relevant diseases:	Fetal growth restriction ( 9 , 15 )

References
1	Gupta MB, et al. (2022) Increased Colocalization and Interaction Between Decidual Protein Kinase A and Insulin-like Growth Factor-Binding Protein-1 in Intrauterine Growth Restriction. J Histochem Cytochem 70, 515-530 35801847 Curated Info
2	Chen AW, et al. (2021) IGFBP-1 hyperphosphorylation in response to nutrient deprivation is mediated by activation of protein kinase Cα (PKCα). Mol Cell Endocrinol 536, 111400 34314739 Curated Info
3	Abu Shehab M, et al. (2020) Inhibition of decidual IGF-1 signaling in response to hypoxia and leucine deprivation is mediated by mTOR and AAR pathways and increased IGFBP-1 phosphorylation. Mol Cell Endocrinol 512, 110865 32502935 Curated Info
4	Singal SS, et al. (2018) Increased Insulin-like Growth Factor Binding Protein-1 Phosphorylation in Decidualized Stromal Mesenchymal Cells in Human Intrauterine Growth Restriction Placentas. J Histochem Cytochem, 22155418772574 29718759 Curated Info
5	Shehab MA, et al. (2017) Exposure of decidualized HIESC to low oxygen tension and leucine deprivation results in increased IGFBP-1 phosphorylation and reduced IGF-I bioactivity. Mol Cell Endocrinol 452, 1-14 28435049 Curated Info
6	Mertins P, et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534, 55-62 27251275 Curated Info
7	Malkani N, et al. (2016) Increased IGFBP-1 phosphorylation in response to leucine deprivation is mediated by CK2 and PKC. Mol Cell Endocrinol 425, 48-60 26733150 Curated Info
8	Damerill I, et al. (2016) Hypoxia Increases IGFBP-1 Phosphorylation Mediated by mTOR Inhibition. Mol Endocrinol 30, 201-16 26714229 Curated Info
9	Malkani N, Jansson T, Gupta MB (2015) IGFBP-1 hyperphosphorylation in response to leucine deprivation is mediated by the AAR pathway. Mol Cell Endocrinol 412, 182-95 25957086 Curated Info
10	Abu Shehab M, et al. (2014) Liver mTOR controls IGF-I bioavailability by regulation of protein kinase CK2 and IGFBP-1 phosphorylation in fetal growth restriction. Endocrinology 155, 1327-39 24437487 Curated Info
11	Bian Y, et al. (2014) An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics 96, 253-62 24275569 Curated Info
12	Britton D, et al. (2014) Quantification of pancreatic cancer proteome and phosphorylome: indicates molecular events likely contributing to cancer and activity of drug targets. PLoS One 9, e90948 24670416 Curated Info
13	Schweppe DK, Rigas JR, Gerber SA (2013) Quantitative phosphoproteomic profiling of human non-small cell lung cancer tumors. J Proteomics 91, 286-96 23911959 Curated Info
14	Abu Shehab M, et al. (2013) Phosphorylation of IGFBP-1 at Discrete Sites Elicits Variable Effects on IGF-I Receptor Autophosphorylation. Endocrinology 154, 1130-43 23354097 Curated Info
15	Abu Shehab M, et al. (2010) Site-specific IGFBP-1 hyper-phosphorylation in fetal growth restriction: clinical and functional relevance. J Proteome Res 9, 1873-81 20143870 Curated Info
16	Abu Shehab M, Inoue S, Han VK, Gupta MB (2009) Site specific phosphorylation of insulin-like growth factor binding protein-1 (IGFBP-1) for evaluating clinical relevancy in fetal growth restriction. J Proteome Res 8, 5325-35 19731965 Curated Info
17	Dolcini L, et al. (2009) Identification of the amniotic fluid insulin-like growth factor binding protein-1 phosphorylation sites and propensity to proteolysis of the isoforms. FEBS J 276, 6033-46 19765076 Curated Info
18	Nissum M, et al. (2009) Functional and complementary phosphorylation state attributes of human insulin-like growth factor-binding protein-1 (IGFBP-1) isoforms resolved by free flow electrophoresis. Mol Cell Proteomics 8, 1424-35 19193607 Curated Info
19	Seferovic MD, et al. (2009) Hypoxia and leucine deprivation induce human insulin-like growth factor binding protein-1 hyperphosphorylation and increase its biological activity. Endocrinology 150, 220-31 18772238 Curated Info
20	Jones JI, Busby WH, Wright G, Clemmons DR (1993) Human IGFBP-1 is phosphorylated on 3 serine residues: effects of site-directed mutagenesis of the major phosphoserine. Growth Regul 3, 37-40 7683525 Curated Info
21	Jones JI, et al. (1993) Identification of the sites of phosphorylation in insulin-like growth factor binding protein-1. Regulation of its affinity by phosphorylation of serine 101. J Biol Chem 268, 1125-31 7678248 Curated Info