Ser738

Site Information
ARIIGEksFRRsVVG SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 448589

In vivo Characterization
Methods used to characterize site in vivo:	[32P] ATP in vitro ( 36 ) , [32P] bio-synthetic labeling ( 59 ) , flow cytometry ( 4 ) , immunoassay ( 16 ) , immunoprecipitation ( 19 , 56 ) , mass spectrometry ( 5 , 6 , 9 , 11 , 12 , 13 , 14 , 15 , 17 , 18 , 20 , 21 , 22 , 23 , 24 , 25 , 27 , 28 , 29 , 31 , 34 , 35 , 37 , 38 , 39 , 40 , 41 , 42 , 46 ) , mutation of modification site ( 16 , 19 , 36 , 47 , 48 , 49 , 51 , 54 , 56 , 59 ) , phospho-antibody ( 3 , 4 , 16 , 19 , 26 , 30 , 32 , 33 , 36 , 43 , 44 , 45 , 47 , 48 , 49 , 50 , 51 , 52 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ) , phosphopeptide mapping ( 59 ) , western blotting ( 3 , 4 , 16 , 19 , 26 , 30 , 32 , 33 , 43 , 47 , 48 , 49 , 50 , 51 , 54 , 55 , 56 , 57 , 58 , 60 )
Disease tissue studied:	breast cancer ( 16 , 57 ) , HER2 positive breast cancer ( 5 ) , luminal A breast cancer ( 5 ) , luminal B breast cancer ( 5 ) , breast cancer, triple negative ( 5 ) , chronic lymphocytic leukemia ( 4 ) , liver cancer ( 26 ) , lung cancer ( 9 , 31 ) , non-small cell lung cancer ( 31 ) , non-small cell lung adenocarcinoma ( 9 ) , pancreatic cancer ( 30 , 60 ) , pancreatic carcinoma ( 30 , 60 ) , rhabdomyosarcoma ( 32 )
Relevant cell line - cell type - tissue:	'muscle, skeletal' ( 33 ) , 293 (epithelial) ( 36 , 43 , 44 , 45 , 50 , 55 , 58 , 59 , 61 ) , A431 (epithelial) [PRKD1 (human)] ( 49 ) , A498 (renal) ( 29 ) , B lymphocyte-blood ( 4 ) , B lymphocyte-spleen ( 50 ) , BAEC (endothelial) ( 52 ) , breast ( 5 ) , COS (fibroblast) ( 47 , 49 , 59 ) , Flp-In T-Rex-293 (epithelial) [PRKD1 (human), genetic knockin] ( 12 ) , Flp-In T-Rex-293 (epithelial) ( 12 ) , HCT116 (intestinal) ( 34 ) , HEK293T (epithelial) ( 19 ) , HeLa (cervical) ( 3 , 6 , 11 , 28 , 35 , 48 , 54 , 56 ) , HeLa S3 (cervical) ( 46 ) , HUES-9 ('stem, embryonic') ( 27 ) , Huh7 (hepatic) ( 26 ) , HUVEC (endothelial) ( 51 , 52 ) , Jurkat (T lymphocyte) ( 13 , 14 , 15 , 17 , 18 , 20 , 21 , 22 , 23 , 24 , 25 , 37 , 38 , 39 , 40 , 41 , 42 ) , lung ( 9 , 31 ) , mast-bone marrow ( 50 ) , MCF-7 (breast cell) ( 16 ) , MDA-MB-435 (breast cell) ( 57 ) , MDA-MB-435S (breast cell) ( 34 ) , MDCK (epithelial) ( 16 ) , MV4-11 (macrophage) ( 34 ) , myocyte-heart ( 19 , 36 ) , NMuMG (epithelial) ( 16 ) , PANC-1 (pancreatic) [PRKD1 (human), transfection] ( 30 ) , PANC-1 (pancreatic) ( 60 ) , PT-67 ( 51 ) , Rh13 (muscle cell) ( 32 ) , SKNDZ (neural crest) ( 49 )

Upstream Regulation
Regulatory protein:	Abl (human) ( 56 ) , AKAP13 (human) ( 43 ) , PKCD (human) ( 56 ) , PRKD1 (human) ( 12 , 30 ) , Src (human) ( 56 )
Putative in vivo kinases:	PKCA (human) ( 45 , 55 ) , PKCD (human) ( 56 ) , PKCH (human) ( 61 ) , PRKD1 (human) ( 36 ) , PRKD3 (human) ( 55 )
Kinases, in vitro:	PKCA (human) ( 59 ) , PKCD (human) ( 56 ) , PKCE (human) ( 56 ) , PKCH (human) ( 61 )
Treatments:	antibody ( 4 , 50 , 53 ) , aphidicolin ( 45 ) , arachidonic_acid ( 57 ) , ATP ( 36 ) , BAPTA-AM ( 51 ) , bisindolylmaleimide ( 60 ) , bombesin ( 47 ) , bradykinin ( 16 ) , BSO ( 56 ) , CID755673 ( 4 ) , colforsin ( 55 ) , DTBR ( 3 ) , EGF ( 16 ) , endothelin ( 19 , 43 ) , exercise ( 33 ) , fibronectin ( 44 ) , GF109203X ( 36 , 45 , 47 ) , Go_6976 ( 26 , 36 , 50 ) , Go_6983 ( 26 , 45 , 47 ) , H-89 ( 45 ) , H2O2 ( 48 , 54 , 56 ) , HB-EGF ( 29 ) , IBMX ( 55 ) , IGF-1 ( 32 ) , isoproterenol ( 19 ) , LPA ( 29 ) , neurotensin ( 30 , 60 ) , nocodazole ( 3 ) , norepinephrine ( 19 , 36 ) , PDGF ( 49 ) , phenylephrine ( 19 , 43 ) , phorbol_ester ( 16 , 19 , 32 , 36 , 49 , 55 , 56 , 58 , 59 , 60 , 61 ) , polyHEMA ( 44 ) , resveratrol ( 54 ) , RO-3306 ( 3 ) , Ro31-8220 ( 45 , 60 ) , salicylate ( 58 ) , STLC ( 3 ) , taxol ( 3 ) , TeTx ( 45 ) , TGF-beta ( 16 ) , thrombin ( 36 ) , U73122 ( 51 ) , U73343 ( 51 ) , vanadate ( 49 , 56 ) , vasopressin ( 47 ) , VEGF ( 51 ) , virus infection ( 26 ) , wortmannin ( 32 , 50 ) , ZM447439 ( 45 )

Downstream Regulation
Effects of modification on PRKD1:	enzymatic activity, induced ( 26 , 47 , 52 , 56 , 59 ) , intracellular localization ( 45 ) , molecular association, regulation ( 52 , 54 , 59 ) , ubiquitination ( 3 )
Effects of modification on biological processes:	cell cycle regulation ( 3 ) , cell differentiation, altered ( 51 ) , cell growth, induced ( 3 ) , cell motility, altered ( 51 ) , signaling pathway regulation ( 3 ) , transcription, altered ( 56 )
Induce interaction with:	ASK1 (human) ( 52 ) , IKKB (human) ( 54 ) , JNK1 (human) ( 59 ) , PKCD (human) ( 54 )

References
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2	Wang F, et al. (2022) Phosphorylation-dependent positive feedback on the oxytocin receptor through the kinase PKD1 contributes to long-term social memory. Sci Signal 15, eabd0033 35104164 Curated Info
3	Pangou E, et al. (2021) A PKD-MFF signaling axis couples mitochondrial fission to mitotic progression. Cell Rep 35, 109129 34010649 Curated Info
4	Saint-Georges S, et al. (2016) Protein kinase D-dependent CXCR4 down-regulation upon BCR triggering is linked to lymphadenopathy in chronic lymphocytic leukaemia. Oncotarget 7, 41031-41046 27127886 Curated Info
5	Mertins P, et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534, 55-62 27251275 Curated Info
6	Sharma K, et al. (2014) Ultradeep human phosphoproteome reveals a distinct regulatory nature of Tyr and Ser/Thr-based signaling. Cell Rep 8, 1583-94 25159151 Curated Info
7	Mertins P, et al. (2014) Ischemia in tumors induces early and sustained phosphorylation changes in stress kinase pathways but does not affect global protein levels. Mol Cell Proteomics 13, 1690-704 24719451 Curated Info
8	Döppler H, et al. (2014) Protein kinase d isoforms differentially modulate cofilin-driven directed cell migration. PLoS One 9, e98090 24840177 Curated Info
9	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
10	Shiromizu T, et al. (2013) Identification of missing proteins in the neXtProt database and unregistered phosphopeptides in the PhosphoSitePlus database as part of the Chromosome-centric Human Proteome Project. J Proteome Res 12, 2414-21 23312004 Curated Info
11	Zhou H, et al. (2013) Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res 12, 260-71 23186163 Curated Info
12	Franz-Wachtel M, et al. (2012) Global detection of protein kinase D-dependent phosphorylation events in nocodazole-treated human cells. Mol Cell Proteomics 11, 160-70 22496350 Curated Info
13	Guo A (2012) CST Curation Set: 13981; Year: 2012; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY] Curated Info
14	Mulhern D (2012) CST Curation Set: 13829; Year: 2012; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: (K/R)XpSX(K/R) Curated Info
15	Mulhern D (2012) CST Curation Set: 13109; Year: 2012; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY] Curated Info
16	Bastea LI, Döppler H, Balogun B, Storz P (2012) Protein Kinase D1 Maintains the Epithelial Phenotype by Inducing a DNA-Bound, Inactive SNAI1 Transcriptional Repressor Complex. PLoS One 7, e30459 22276203 Curated Info
17	Mulhern D (2011) CST Curation Set: 13106; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY]) Curated Info
18	Mulhern D (2011) CST Curation Set: 13110; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Curated Info
19	Phan D, Stratton MS, Huynh QK, McKinsey TA (2011) A novel protein kinase C target site in protein kinase D is phosphorylated in response to signals for cardiac hypertrophy. Biochem Biophys Res Commun 411, 335-41 21726532 Curated Info
20	Guo A (2011) CST Curation Set: 11887; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P Curated Info
21	Guo A (2011) CST Curation Set: 11888; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P Curated Info
22	Guo A (2011) CST Curation Set: 11890; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY] Curated Info
23	Guo A (2011) CST Curation Set: 11891; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY] Curated Info
24	Guo A (2011) CST Curation Set: 11892; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY] Curated Info
25	Guo A (2011) CST Curation Set: 11893; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY] Curated Info
26	Amako Y, Syed GH, Siddiqui A (2011) Protein Kinase D Negatively Regulates Hepatitis C Virus Secretion through Phosphorylation of Oxysterol-binding Protein and Ceramide Transfer Protein. J Biol Chem 286, 11265-74 21285358 Curated Info
27	Rigbolt KT, et al. (2011) System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal 4, rs3 21406692 Curated Info
28	Kettenbach AN, et al. (2011) Quantitative phosphoproteomics identifies substrates and functional modules of aurora and polo-like kinase activities in mitotic cells. Sci Signal 4, rs5 21712546 Curated Info
29	Schreiber TB, et al. (2010) An integrated phosphoproteomics work flow reveals extensive network regulation in early lysophosphatidic acid signaling. Mol Cell Proteomics 9, 1047-62 20071362 Curated Info
30	Kisfalvi K, Hurd C, Guha S, Rozengurt E (2010) Induced overexpression of protein kinase D1 stimulates mitogenic signaling in human pancreatic carcinoma PANC-1 cells. J Cell Physiol 223, 309-16 20082306 Curated Info
31	Rikova K (2010) CST Curation Set: 9452; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY]) Curated Info
32	Thimmaiah KN, Easton JB, Houghton PJ (2010) Protection from rapamycin-induced apoptosis by insulin-like growth factor-I is partially dependent on protein kinase C signaling. Cancer Res 70, 2000-9 20179209 Curated Info
33	McGee SL, Fairlie E, Garnham AP, Hargreaves M (2009) Exercise-induced histone modifications in human skeletal muscle. J Physiol 587, 5951-8 19884317 Curated Info
34	Oppermann FS, et al. (2009) Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics 8, 1751-64 19369195 Curated Info
35	Chen RQ, et al. (2009) CDC25B mediates rapamycin-induced oncogenic responses in cancer cells. Cancer Res 69, 2663-8 19276368 Curated Info
36	Rybin VO, Guo J, Steinberg SF (2009) Protein kinase D1 autophosphorylation via distinct mechanisms at Ser744/Ser748 and Ser916. J Biol Chem 284, 2332-43 19029298 Curated Info
37	Zhou J (2009) CST Curation Set: 5901; Year: 2009; Biosample/Treatment: cell line, Jurkat/TPA; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: (K/R)XpSX(K/R)Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Ser) PKC Substrate Antibody Cat#: 2261, PTMScan(R) Phospho-PKC Substrate Motif (K/RXpSXK/R) Immunoaffinity Beads Cat#: 1985 Curated Info
38	Zhou J (2009) CST Curation Set: 5899; Year: 2009; Biosample/Treatment: cell line, Jurkat/untreated; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: (K/R)XpSX(K/R)Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Ser) PKC Substrate Antibody Cat#: 2261, PTMScan(R) Phospho-PKC Substrate Motif (K/RXpSXK/R) Immunoaffinity Beads Cat#: 1985 Curated Info
39	Zhou J (2009) CST Curation Set: 5900; Year: 2009; Biosample/Treatment: cell line, Jurkat/TPA; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: (K/R)XpSX(K/R)Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Ser) PKC Substrate Antibody Cat#: 2261, PTMScan(R) Phospho-PKC Substrate Motif (K/RXpSXK/R) Immunoaffinity Beads Cat#: 1985 Curated Info
40	Zhou J (2009) CST Curation Set: 5896; Year: 2009; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: (K/R)XpSX(K/R)Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Ser) PKC Substrate Antibody Cat#: 2261, PTMScan(R) Phospho-PKC Substrate Motif (K/RXpSXK/R) Immunoaffinity Beads Cat#: 1985 Curated Info
41	Zhou J (2009) CST Curation Set: 5898; Year: 2009; Biosample/Treatment: cell line, Jurkat/untreated; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: (K/R)XpSX(K/R)Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Ser) PKC Substrate Antibody Cat#: 2261, PTMScan(R) Phospho-PKC Substrate Motif (K/RXpSXK/R) Immunoaffinity Beads Cat#: 1985 Curated Info
42	Zhou J (2009) CST Curation Set: 5897; Year: 2009; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: (K/R)XpSX(K/R)Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Ser) PKC Substrate Antibody Cat#: 2261, PTMScan(R) Phospho-PKC Substrate Motif (K/RXpSXK/R) Immunoaffinity Beads Cat#: 1985 Curated Info
43	Carnegie GK, et al. (2008) AKAP-Lbc mobilizes a cardiac hypertrophy signaling pathway. Mol Cell 32, 169-79 18951085 Curated Info
44	Biliran H, et al. (2008) Protein kinase D is a positive regulator of Bit1 apoptotic function. J Biol Chem 283, 28029-37 18703509 Curated Info
45	Papazyan R, et al. (2008) Protein kinase D isozymes activation and localization during mitosis. Exp Cell Res 314, 3057-68 18692497 Curated Info
46	Daub H, et al. (2008) Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell 31, 438-48 18691976 Curated Info
47	Jacamo R, et al. (2008) Sequential protein kinase C (PKC)-dependent and PKC-independent protein kinase D catalytic activation via Gq-coupled receptors: differential regulation of activation loop Ser(744) and Ser(748) phosphorylation. J Biol Chem 283, 12877-87 18337243 Curated Info
48	Döppler H, Storz P (2007) A novel tyrosine phosphorylation site in protein kinase D contributes to oxidative stress-mediated activation. J Biol Chem 282, 31873-81 17804414 Curated Info
49	Johannessen M, et al. (2007) Protein kinase D induces transcription through direct phosphorylation of the cAMP-response element-binding protein. J Biol Chem 282, 14777-87 17389598 Curated Info
50	Lessmann E, et al. (2007) Oxysterol-binding protein-related protein (ORP) 9 is a PDK-2 substrate and regulates Akt phosphorylation. Cell Signal 19, 384-92 16962287 Curated Info
51	Qin L, Zeng H, Zhao D (2006) Requirement of protein kinase D tyrosine phosphorylation for VEGF-A165-induced angiogenesis through its interaction and regulation of phospholipase Cgamma phosphorylation. J Biol Chem 281, 32550-8 16891660 Curated Info
52	Zhang W, Zheng S, Storz P, Min W (2005) Protein kinase D specifically mediates apoptosis signal-regulating kinase 1-JNK signaling induced by H2O2 but not tumor necrosis factor. J Biol Chem 280, 19036-44 15755722 Curated Info
53	Chan SM, et al. (2004) Protein microarrays for multiplex analysis of signal transduction pathways. Nat Med 10, 1390-6 15558056 Curated Info
54	Storz P, Döppler H, Toker A (2004) Activation loop phosphorylation controls protein kinase D-dependent activation of nuclear factor kappaB. Mol Pharmacol 66, 870-9 15226414 Curated Info
55	Carnegie GK, et al. (2004) AKAP-Lbc nucleates a protein kinase D activation scaffold. Mol Cell 15, 889-99 15383279 Curated Info
56	Storz P, Döppler H, Toker A (2004) Protein kinase Cdelta selectively regulates protein kinase D-dependent activation of NF-kappaB in oxidative stress signaling. Mol Cell Biol 24, 2614-26 15024053 Curated Info
57	Kennett SB, Roberts JD, Olden K (2004) Requirement of protein kinase C micro activation and calpain-mediated proteolysis for arachidonic acid-stimulated adhesion of MDA-MB-435 human mammary carcinoma cells to collagen type IV. J Biol Chem 279, 3300-7 14607845 Curated Info
58	Jiang G, et al. (2003) Salicylic acid reverses phorbol 12-myristate-13-acetate (PMA)- and tumor necrosis factor alpha (TNFalpha)-induced insulin receptor substrate 1 (IRS1) serine 307 phosphorylation and insulin resistance in human embryonic kidney 293 (HEK293) cells. J Biol Chem 278, 180-6 12409308 Curated Info
59	Hurd C, Waldron RT, Rozengurt E (2002) Protein kinase D complexes with C-Jun N-terminal kinase via activation loop phosphorylation and phosphorylates the C-Jun N-terminus. Oncogene 21, 2154-60 11948398 Curated Info
60	Guha S, Rey O, Rozengurt E (2002) Neurotensin induces protein kinase C-dependent protein kinase D activation and DNA synthesis in human pancreatic carcinoma cell line PANC-1. Cancer Res 62, 1632-40 11912133 Curated Info
61	Brändlin I, et al. (2002) Protein kinase C (PKC)eta-mediated PKC mu activation modulates ERK and JNK signal pathways. J Biol Chem 277, 6490-6 11741879 Curated Info