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Phosphorylation mapping of Laminin β1-chain: Kinases in association with active sites

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Abstract

Laminins are a major constituent of the extracellular matrix (ECM). Laminin-111, the most extensively studied laminin isoform, consists of the α1, the β1 and the γ1 chain, and is involved in many cellular processes, like adhesion, migration and differentiation. Given the regulatory role of phosphorylation in protein function, it is important to identify the phosphorylation sites of human laminin β1-chain sequence (LAMB1). Therefore, we computationally predicted all possible phosphorylation sites in LAMB1. For the first time, we identified the possibly responsible kinases for already in vitro experimentally observed phosphorylated residues in LAMB1. All known functional (active) sites of LAMB1, were recorded after an extensive literature search and combined with the experimentally observed and our predicted phosphorylated residues. This generated a detailed phosphorylation map of LAMB1. Five kinases (PKA, PKC, CKII, CKI and GPCR1) were indicated important, while the role of PKA, PKC and CKII, kinases known for ecto-phosphorylation activity, was highlighted. The activity of PKA and PKC was associated with the active site RIQNLLKITNLRIKFVKLHTLGDNLLDS. Also, predicted phosphorylations inside two amyloidogenic (DSITKYFQMSLE, VILQHSAADIAR) and two anti-cancerous (YIGSR and PDSGR) sites suggested a possible role in the development of the corresponding diseases.

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Abbreviations

AD:

Alzheimer disease

Akt:

Ak strain transforming (alternative name, protein kinase B)

ALK:

anaplastic lymphoma kinase

AMPK:

5′ adenosine monophosphate-activated protein kinase

APP:

β–amyloid precursor protein

ATM:

ataxia telangiectasia mutated

Aβ:

amyloid-β peptides

BARK1:

beta-adrenergic receptor kinase

CaMKII:

calmodulin-dependent kinase II

CaMKIV:

calmodulin-dependent kinase IV

CDK5:

cyclin-dependent kinase 5

Chk1:

checkpoint kinase 1

CKI:

casein kinase I

CKII:

casein kinase II

CLK1:

dual specificity protein kinase CLK1 (alternative name, CDC-like kinase 1)

COB:

cobblestone brain malformation

DNA-PK:

deoxyribonucleic acid protein kinase

ECM:

extracellular matrix

EGFR:

epidermal growth factor receptor

ERK1:

extracellular signal-regulated kinase 1

ERK2:

extracellular signal-regulated kinase 2

GPCR1:

G-coupled protein receptor 1

GSK-3:

glycogen synthase kinase-3

H1K:

growth-associated histone H1 kinase

HTP:

high-throughput (option in PhosphositePlus®)

JAK2:

janus kinase 2

La/SSB:

Sjögren syndrome type B antigen (alternative name, lupus La protein)

MAPKAPK1:

mitogen-activated protein (MAP) kinase-activated protein kinase 1

MAPKAPK2:

mitogen-activated protein (MAP) kinase-activated protein kinase 2

MMP-2:

matrix metalloproteinase-2

ONH:

optic nerve hypoplasia

p70S6K:

ribosomal protein S6 kinase

PAK2:

P21 (RAC1) activated kinase 2

PDGFRα:

platelet-derived growth factor receptor alpha

PDK:

pyruvate dehydrogenase kinase

PKA:

protein kinase A

PKC:

protein kinase C

PLK1:

polo-like kinase 1

PO3 2− :

phosphoryl group

PO4 3− :

phosphate group

PTKs:

protein tyrosine kinases

PTM:

post-translational modification

References

  • Altschul S, Gish W, Miller W, Myers E and Lipman D 1990 Basic local alignment search tool. J. Mol. Biol. 215 403–410

    CAS  PubMed  Google Scholar 

  • Amanchy R, Periaswamy B, Mathivanan S, Reddy R, Tattikota SG and Pandey A 2007 A compendium of curated phosphorylation-based substrate and binding motifs. Nat. Biotechnol. 25 285–286

    CAS  PubMed  Google Scholar 

  • Apasov SG, Smith PT, Jelonek MT, Margulies DH and Sitkovsky MV 1996 Phosphorylation of extracellular domains of T-lymphocyte surface proteins. Constitutive serine and threonine phosphorylation of the T cell antigen receptor ectodomains. J. Biol. Chem. 271 25677–25683

    CAS  PubMed  Google Scholar 

  • Ashcroft M, Kubbutat MH and Vousden KH 1999 Regulation of p53 function and stability by phosphorylation. Mol. Cel. Biol. 19 1751–1758

    CAS  Google Scholar 

  • Aumailley M, Bruckner-Tuderman L, Carter WG, Deutzmann R, Edgar D, Ekblom P and Yurchenco PD 2005 A simplified laminin nomenclature. Matrix Biol. 24 326–332

    CAS  PubMed  Google Scholar 

  • Babiker AA, Ronquist G, Nilsson B and Ekdahl KN 2006 Overexpression of ecto-protein kinases in prostasomes of metastatic cell origin. Prostate 66 675–686

    CAS  PubMed  Google Scholar 

  • Babinska A, Ehrlich YH and Kornecki E 1996 Activation of human platelets by protein kinase C antibody: Role for surface phosphorylation in homeostasis. Am. J. Physiol. 271 H2134–H2144

    CAS  PubMed  Google Scholar 

  • Beck K, Hunter I and Engel J 1990 Structure and function of laminin: anatomy of a multidomain glycoprotein. FASEB J. 4 148–160

    CAS  PubMed  Google Scholar 

  • Berthel J, Sutherland EW and Rall TW 1957 The relationship of epinephrine and glucagon to liver phosphorylase. IV. Effect of epinephrine and glucagon on the reactivation of phosphorylase in liver homogenates. J. Biol. Chem. 224 463–475

    Google Scholar 

  • Bohana-Kashtan O, Pinna LA and Fishelson Z 2005 Extracellular phosphorylation of C9 by protein kinase CK2 regulates complement-mediated lysis. Eur. J. Immunol. 35 1939–1948

    CAS  PubMed  Google Scholar 

  • Bronfman F, Alvarez A, Morgan C and Inestrosa N 1998 Laminin blocks the assembly of wild-type Aβ and the Dutch variant peptide into Alzheimer’s fibrils. Amyloid 5 16–23

    CAS  PubMed  Google Scholar 

  • Bronfman F, Garrido J, Alvarez A, Morgan C and Inestrosa N 1996 Laminin inhibits amyloid-β-peptide fibrillation. Neurosci. Lett. 218 201–203

    CAS  PubMed  Google Scholar 

  • Brooks P, Strömblad S, Sanders L, von Schalscha T, Aimes R, Stetler-Stevenson W, Quigley JP and Cheresh DA 1996 Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin αvβ3. Cell 85 683–693

    Article  CAS  PubMed  Google Scholar 

  • Bruckner-Tuderman L and Bruckner P 1998 Genetic diseases of the extracellular matrix: more than just connective tissue disorders. J. Mol. Med. 76 226–237

    CAS  PubMed  Google Scholar 

  • Canese K and Weis S 2002 PubMed: The Bibliographic Database; in The NCBI Handbook (second ed) (Bethesda (MD): National Center for Biotechnology Information) https://www.ncbi.nlm.nih.gov/pubmed

  • Chakraborti S, Chakraborti T and Dhalla N 2017 Proteases in human diseases. (Singapore: Springer Verlag)

    Google Scholar 

  • Charonis AS, Skubitz APN, Koliakos G, Reger LA, Dege J, Vogel AM, Wohlhueter R and Furcht LT 1988 A novel synthetic peptide from the B1 chain of laminin with heparin-binding and cell adhesion-promoting activities. J.Cell Biol. 107 1253–1260

    CAS  PubMed  Google Scholar 

  • Colognato H and Yurchenco P 2000 Form and function: the laminin family of heterotrimers. Dev. Dyn. 218 213–234

    CAS  PubMed  Google Scholar 

  • Cori GT and Cori CF 1945 The enzymatic conversion of phosphorylase a to b. J. Biol. Chem. 158 321–332

    CAS  Google Scholar 

  • Cori GT and Green AA 1943 Crystalline muscle phosphorylase II. Prosthetic group. J. Biol. Chem. 151 31–38

    CAS  Google Scholar 

  • Devisme L, Bouchet C, Gonzalès M, Alanio E, Bazin A, Bessières B, Bigi N, Blanchet P, et al. 2012 Cobblestone lissencephaly: neuropathological subtypes and correlations with genes of dystroglycanopathies. Brain 135 469–482

    PubMed  Google Scholar 

  • Dubey PK, Singodia D and Vyas SP 2010 Liposomes modified with YIGSR peptide for tumor targeting. J. Drug Target. 18 373–380

    Google Scholar 

  • Dusenbery K, Mendiola J and Skubitz KM 1988 Evidence for ecto-protein kinase activity on the surface of human neutrophils. Biochem. Biophys. Res. Commun. 153 7–13

    CAS  PubMed  Google Scholar 

  • Ehrlich Y, Davis T, Bock E, Kornecki E and Lenox R 1986 Ecto-protein kinase activity on the external surface of neural cells. Nature 320 67–70

    CAS  PubMed  Google Scholar 

  • Eisenberg D and Jucker M 2012 The Amyloid State of Proteins in Human Diseases. Cell 148 1188–1203

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ekblom M, Falk M, Salmivirta K, Durbeej M and Ekblom P 1998 Laminin isoforms and epithelial development. Ann. N.Y. Acad. Sci. 857 194–211

    CAS  PubMed  Google Scholar 

  • Ekblom P, Lonai P and Talts JF 2003 Expression and biological role of laminin-1. Matrix Biol. 22 35–47

    CAS  PubMed  Google Scholar 

  • Engel J, Odermatt E, Engel A, Madri J, Furthmayr H, Rohde H and Timpl R 1981 Shapes, domain organizations and flexibility of laminin and fibronectin, two multifunctional proteins of the extracellular matrix. J. Mol. Biol. 150 97–120

    Google Scholar 

  • Fischer A 1946 Mechanism of the proteolytic activity of malignant tissue cells. Nature 157 442–442

    CAS  PubMed  Google Scholar 

  • Fowler D, Koulov A, Balch W and Kelly J 2007 Functional amyloid – from bacteria to humans. Trends Biochem. Sci. 32 217–224

    CAS  PubMed  Google Scholar 

  • Gandy S, Czernik A and Greengard P 1988 Phosphorylation of Alzheimer disease amyloid precursor peptide by protein kinase C and Ca2+/calmodulin-dependent protein kinase II. Proc. Natl. Acad. Sci. USA 85 6218–6221

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gauci S, Helbig A, Slijper M, Krijgsveld J, Heck A and Mohammed S 2009 Lys-N and Trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal. Chem. 81 4493–4501

    CAS  PubMed  Google Scholar 

  • Geberhiwot T and Skoglund G 1997 Cell surface and serum protein phosphorylation by U-937 cell ectoprotein kinases. Biochem. Mol. Biol. Int. 41 269–278

    CAS  PubMed  Google Scholar 

  • Giannelli G, Falk-Marzillier J, Schiraldi O, Stetler-Stevenson W and Quaranta V 1997 Induction of cell migration by matrix metalloprotease-2 cleavage of laminin-5. Science 277 225–228

    CAS  PubMed  Google Scholar 

  • Govaere O, Petz M, Wouters J, Vandewynckel Y, Scott E, Topal B, Nevens F, Verslype C, Anstee QM, Van Vlierberghe H, Mikulits W and Roskams T 2017 The PDGFRα-laminin B1-keratin 19 cascade drives tumor progression at the invasive front of human hepatocellular carcinoma. Oncogene 36 6605–6616

    Google Scholar 

  • Graf J, Iwamoto Y, Sasaki M, Martin GR, Kleinman HK, Robey FA and Yamada Y 1987b Identification of an amino acid sequence in laminin mediating cell attachment, chemotaxis, and receptor binding. Cell 48 989–996

    Google Scholar 

  • Graf J, Ogle RC, Robey FA, Sasaki M, Martin GR, Yamada Y and Kleinman HK 1987a A pentapeptide from the laminin B1 chain mediates cell adhesion and binds the 67000 laminin receptor. Biochemistry 26 6896–6900

    CAS  PubMed  Google Scholar 

  • Grant D, Tashiro K, Segui-Real B, Yamada Y, Martin G and Kleinman HK 1989 Two different laminin domains mediate the differentiation of human endothelial cells into capillary-like structures in vitro. Cell 58 933–943

    CAS  PubMed  Google Scholar 

  • Haass C 1999 The presenilins in Alzheimer’s disease–proteolysis holds the key. Science 286 916–919

    CAS  PubMed  Google Scholar 

  • Haass C and Selkoe DJ 2007 Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid beta-peptide. Nat. Rev. Mol. Cell Biol. 8 101–112

    CAS  PubMed  Google Scholar 

  • Hogan MV, Pawlowska Z, Yang HA, Kornecki E and Ehrlich YH 1995 Surface phosphorylation by ecto-protein kinase C in brain neurons: a target for Alzheimer’s beta-amyloid peptides. J. Neurochem. 65 2022–2030

    CAS  PubMed  Google Scholar 

  • Hohenester E and Yurchenco PD 2013 Laminins in basement membrane assembly. Cell Adhes. Migr. 7 56–63

    PubMed  PubMed Central  Google Scholar 

  • Hopker VH, Shewan D, Tessier-Lavigne M, Poo M and Holt C 1999 Growth-cone attraction to netrin-1 is converted to repulsion by laminin-1. Nature 401 69–73

    CAS  PubMed  Google Scholar 

  • Hornbeck PV, Zhang B, Murray B, Kornhauser JM, Latham V and Skrzypek E 2014 PhosphoSitePlus: mutations, PTMs and recalibrations. Nucleic Acids Res. 43 D512–D520

    PubMed  PubMed Central  Google Scholar 

  • Hsu P, Kang S, Rameseder J, Zhang Y, Ottina K, Lim D, Peterson T, Choi Y, Gray N, Yaffe M, Marto J and Sabatini D 2011 The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling. Science 332 1317–1322

    CAS  PubMed  PubMed Central  Google Scholar 

  • Imada S, Sugiyama Y and Imada M 1988 Fibronectin phosphorylation by ecto-protein kinase. Exp. Cell Res. 179 554–564

    CAS  PubMed  Google Scholar 

  • Iwamoto Y, Nomizu M, Yamada Y, Ito Y, Tanaka K and Sugioka Y 1996 Inhibition of angiogenesis, tumour growth and experimental metastasis of human fibrosarcoma cells HT1080 by a multimeric form of the laminin sequence Tyr-lle-Gly-Ser-Arg (YIGSR). Br. J. Cancer 73 589–595

    CAS  PubMed  PubMed Central  Google Scholar 

  • Iwamoto Y, Robey FA, Graf J, Sasaki M, Kleinman HK, Yamada Y and Martin GR 1987 YIGSR, a synthetic laminin pentapeptide, inhibits experimental metastasis formation. Science 238 1132–134

    CAS  PubMed  Google Scholar 

  • Kasai S, Urushibata S, Hozumi K, Yokoyama K, Ichikawa N, Kadoya Y, Nishi N, Watanabe N, Yamada Y and Nomizu M 2007 Identification of multiple amyloidogenic sequences in laminin-1. Biochemistry 46 3966–3974

    CAS  PubMed  Google Scholar 

  • Khoury GA, Baliban RC and Floudas CA 2011 Proteome-wide post-translational modification statistics: frequency analysis and curation of the Swiss-prot database. Sci. Rep. 1 90

    CAS  PubMed Central  Google Scholar 

  • Kibbey MC, Jucker M, Weeks BS, Neve RL, Van Nostrand WE and Kleinman HK 1993 Amyloid precursor protein binds to the neurite-promoting IKVAV site of laminin. Proc. Natl. Acad. Sci. USA 90 10150–10153

    Google Scholar 

  • Klammer M, Kaminski M, Zedler A, Oppermann F, Blencke S, Marx S, Müller S, Tebbe A, Godl K and Schaab C 2012 phosphosignature predicts dasatinib response in non-small cell lung cancer. Mol. Cell. Proteomics 11 651–668

    Google Scholar 

  • Kleinman H, Graf J, Iwamoto Y, Sasaki M, Schasteen C, Yamada Y, Martin G and Robey F 1989 Identification of a second active site in laminin for promotion of cell adhesion and migration and inhibition of in vivo melanoma lung colonization. Arch. Biochem. Biophys. 272 39–45

    CAS  PubMed  Google Scholar 

  • Koliakos G, Kouzi-Koliakos K, Triantos A, Trachana V, Kavoukopoulos E, Gaitatzi M and Dimitriadou A 2000 Laminin-1 phosphorylation by protein kinase A: effect on self assembly and heparin binding. J. Biochem. Mol. Biol. 33 370–378

    CAS  Google Scholar 

  • Koliakos G, Trachana V, Gaitatzi M and Dimitriadou A 2001 Phosphorylation of laminin-1 by protein kinase C. Mol. Cells 11 179–185

    CAS  PubMed  Google Scholar 

  • Koliakos G, Trontzos C, Kouzi-Koliakos K, Kanellaki M and Grammaticos P 1997 Lung carcinoma imaging using a synthetic laminin derivative radioiodinated peptide YIGSR. J. Nucl. Med. 38 1940–1994

    CAS  PubMed  Google Scholar 

  • Kondrashin A, Nesterova M and Cho-Chung Y 1999 Cyclic Adenosine 3′:5′-monophosphate dependent protein kinase on the external surface of LS-174T human colon carcinoma cells. Biochemistry 38 172–179

    CAS  PubMed  Google Scholar 

  • Kouzi-Koliakos K, Koliakos G, Trontzos C, Papageorgiou A, Iliadis S, Triantos A, Dimitriadou A and Kanellaki M 1996 In vivo binding of the radioiodinated peptide YIGSR on B16 melanoma cells. Invasion Metastasis 16 322–329

    CAS  PubMed  Google Scholar 

  • Kouzi-Koliakos K, Koliakos GG, Tsilibary EC, Furcht LT and Charonis AS 1989 Mapping of three major heparin-binding sites on laminin and identification of a novel heparin-binding site on the B1 chain. J. Biol. Chem. 264 17971–17978

    CAS  PubMed  Google Scholar 

  • Krebs EG and Fischer EH 1956 The phosphorylase b to a converting enzyme of rabbit skeletal muscle. Biochim. Biophys. Acta 20 150–157

    CAS  PubMed  Google Scholar 

  • Krebs EG, Graves DJ and Fischer EH 1959 Factors affecting the activity of muscle phosphorylase b kinase. J. Biol. Chem. 234 2867–2873

    CAS  PubMed  Google Scholar 

  • Kumar S and Walter J 2011 Phosphorylation of amyloid beta (Aβ) peptides – A trigger for formation of toxic aggregates in Alzheimer’s disease. Aging 3 803–812

    PubMed  PubMed Central  Google Scholar 

  • Kumar S, Rezaei-Ghaleh N, Terwel D, Thal DR, Richard M, Hoch M, Mc Donald JM, Wüllner U, Glebov K, Heneka MT, Walsh DM, Zweckstetter M and Walter J 2011 Extracellular phosphorylation of the amyloid-β peptide promotes formation of toxic aggregates during the pathogenesis of Alzheimer disease. EMBO J. 30 2255–2265

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kumar S, Singh S, Hinze D, Josten M, Sahl H, Siepmann M and Walter J 2012 Phosphorylation of amyloid-β peptide at serine 8 attenuates its clearance via insulin-degrading and angiotensin-converting enzymes. J. Biol. Chem. 287 8641–8651

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lee H, Na K, Kwon M, Kim H, Kim K and Paik Y 2009 Quantitative analysis of phosphopeptides in search of the disease biomarker from the hepatocellular carcinoma specimen. Proteomics 9 3395–3408

    CAS  PubMed  Google Scholar 

  • Li S, Harrison D, Carbonetto S, Fässler R, Smyth N, Edgar D and Yurchenco P 2002 Matrix assembly, regulation, and survival functions of laminin and its receptors in embryonic stem cell differentiation. J. Cell Biol. 157 1279–1290

    CAS  PubMed  PubMed Central  Google Scholar 

  • Li Y 2011 [dataset] CST Curation Set: 10527; Year: 2011; Biosample/Treatment: tissue, heart/untreated; Disease: ventricular tachycardia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991

  • Liesi P, Narvlnen A, Soos J, Sariola H and Snounou G 1989 Identification of a neurite outgrowth-promoting domain of laminin using synthetic peptides. FEBS Lett. 244 141–148

    CAS  PubMed  Google Scholar 

  • Lodish H, Berk A, Matsudaira P, Kaiser CA, Krieger M, Scott MP, Zipursky SL and Darnell J 2000 Integrating cells into tissues; in Molecular Cell Biology (fifth ed) (New York: WH Freeman and Company) pp 197–234

  • Lopez-Barcons LA, Polo D, Reig F and Fabra A 2004 Pentapeptide YIGSR-mediated HT-1080 fibrosarcoma cells targeting of adriamycin encapsulated in sterically stabilized liposomes. Biomed. Mater. Res. A. 69 155–163.

    CAS  Google Scholar 

  • Lundby A, Andersen M, Steffensen A, Horn H, Kelstrup C, Francavilla C, Jensen LJ, Schmitt N, Thomsen MB and Olsen, JV 2013 In vivo phosphoproteomics analysis reveals the cardiac targets of adrenergic receptor signaling. Sci. Signal. 6 rs11

    PubMed  Google Scholar 

  • Malinda KM, Nomizu M, Chung M, Delgado M, Kuratoni Y, Yamada Y, Kleinman HK and Ponce ML 1999 Identification of laminin a1 and b1 chain peptides active for endothelial cell adhesion, tube formation, and aortic sprouting. FASEB J. 13 53–62

    CAS  PubMed  Google Scholar 

  • Mecham R 1991 Laminin receptors. Annu. Rev. Cell Dev. Biol. 7 71–91

    CAS  Google Scholar 

  • Mecham RP, Hinek A, Griffin GL, Senior RM and Liotta LA 1989 The elastin receptor shows structural and functional similarities to the 67-kDa tumor cell laminin receptor. J. Biol. Chem. 264 16652–16657

    CAS  PubMed  Google Scholar 

  • Mertins P, Mani D, Ruggles K, Gillette M, Clauser K, Wang P, Wang X, Qiao JW, et al. 2016 Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534 55–62

    CAS  PubMed  PubMed Central  Google Scholar 

  • Miner JH, Li C, Mudd JL, Go G and Sutherland A 2004 Compositional and structural requirements for laminin and basement membranes during mouse embryo implantation and gastrulation. Development 131 2247–2256

    CAS  PubMed  Google Scholar 

  • Ming GL, Song HJ, Berninger B, Holt CE, Tessier-Lavigne M and Poo MM 1997 cAMP-dependent growth cone guidance by netrin-1. Neuron 19 1225–1235

    CAS  PubMed  Google Scholar 

  • Morgan C, Bugueño M, Garrido J and Inestrosa N 2002 Laminin affects polymerization, depolymerization and neurotoxicity of Aβ peptide. Peptides 23 1229–1240

    CAS  PubMed  Google Scholar 

  • Murata J, Saiki I, Azuma I and Nishi N 1989 Inhibitory effect of a synthetic polypeptide, poly(Tyr-Ile-Gly-Ser-Arg), on the metastatic formation of malignant tumour cells. Int. J. Biol. Macromol. 11 97–99

    CAS  PubMed  Google Scholar 

  • Murtomaki S, Risteli J, Risteli L, Koivisto UM, Johansson S and Liesi P 1992 Laminin and its neurite outgrowth- promoting domain in the brain in Alzheimer’ s disease and Down’ s syndrome patients. J. Neurosci. Res. 32 261–273

    CAS  PubMed  Google Scholar 

  • Nakai M, Mundy GR, Williams PJ, Boyce B and Yoneda, T 1992. A synthetic antagonist to laminin inhibits the formation of osteolytic metastases by human melanoma cells in nude mice. Cancer Res. 52 5395–5399

    CAS  PubMed  Google Scholar 

  • Narindrasorasak S, Lowery DE, Altman RA, Gonzalez-DeWhitt PA, Greenberg BD and Kisilevsky R 1992 Characterization of high affinity binding between laminin and Alzheimer’s disease amyloid precursor proteins. Lab. Investig. 67 643–652

    Google Scholar 

  • Nomizu M, Kuratomi Y, Ponce M, Song S, Miyoshi K, Otaka A, Powell S, Hoffman M, Kleinman HK and Yamada Y 2000 Cell adhesive sequences in mouse laminin β1 chain. Arch. Biochem. Biophys. 378 311–320

    CAS  PubMed  Google Scholar 

  • O’Leary N, Wright M, Brister J, Ciufo S, Haddad D, McVeigh R, Rajput B, Robbertse B, et al. 2015 Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation. Nucleic Acids Res. 44 D733–D745

    PubMed  PubMed Central  Google Scholar 

  • Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P and Mann M 2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 127 635–648

    CAS  PubMed  Google Scholar 

  • Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller M, Jensen L, Nigg EA, Brunak S and Mann M 2010 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. 3 ra3

    PubMed  Google Scholar 

  • Ott U, Odermatt E, Engel J, Furthmayr H and Timpl R 1982 Protease resistance and conformation of laminin. Eur. J. Biochem. 123 63–72

    CAS  PubMed  Google Scholar 

  • Perlmutter LS, Barron E, Saperia D and Chui HC 1991. Association between vascular basement membrane components and the lesions of Alzheimer’s disease. J. Neurosci. Res. 30 673–681

    CAS  PubMed  Google Scholar 

  • Petz M, Kozina D, Huber H, Siwiec T, Seipelt J, Sommergruber W and Mikulits W 2007 The leader region of Laminin B1 mRNA confers cap-independent translation. Nucleic Acids Res. 35 2473–2482

    CAS  PubMed  PubMed Central  Google Scholar 

  • Plopper G 2007 The extracellular matrix and cell adhesion; in Cells (eds) B Lewin, L Cassimeris, V Lingappa and G Plopper (Sudbury, MA: Jones and Bartlett)

    Google Scholar 

  • Powell SK, Rao J, Roque E, Nomizu M, Kuratomi Y, Yamada Y and Kleinman HK 2000 Neural cell response to multiple novel sites on laminin-1. J. Neurosci. Res. 61 302–312

    CAS  PubMed  Google Scholar 

  • Pruitt KD, Harrow J, Harte RA, Wallin C, Diekhans M, Maglott DR, Searle S, Farrell CM, et al. 2009 The consensus coding sequence (CCDS) project: Identifying a common protein-coding gene set for the human and mouse genomes. Genome Res. 19 1316–1323

    CAS  PubMed  PubMed Central  Google Scholar 

  • Radmanesh F, Caglayan A, Silhavy J, Yilmaz C, Cantagrel V, Omar T, Rosti B, Kaymakcalan H, Gabriel S, Li M, Sestan N, Bilguvar K, Dobyns W, Zaki M, Gunel M and Gleeson J 2013 Mutations in LAMB1 cause cobblestone brain malformation without muscular or ocular abnormalities. Am. J. Hum. Genet. 92 468–474

    CAS  PubMed  PubMed Central  Google Scholar 

  • Raijmakers R, Kraiczek K, de Jong A, Mohammed S and Heck A 2010 Exploring the human leukocyte phosphoproteome using a microfluidic reversed-phase-TiO2-reversed-phase high-performance liquid chromatography phosphochip coupled to a quadrupole time-of-flight mass spectrometer. Anal. Chem. 82 824–832

    CAS  PubMed  Google Scholar 

  • Rakash S, Rana F, Rafiq S, Masood A and Amin S 2012 Role of proteases in cancer: a review. Biotechnol. Mol. Biol. Rev. 7 90–101

    Google Scholar 

  • Rao CN, Castronovo, V, Schmitt MC, Wewer UM, Claysmith AP, Liotta LA and Sobel ME 1989 Evidence for a precursor of the high-affinity metastasis-associated murine laminin receptor. Biochemistry 28 7476–7486

    CAS  PubMed  Google Scholar 

  • Rigbolt K, Prokhorova T, Akimov V, Henningsen J, Johansen P, Kratchmarova I, Kassem M, Mann M, Olsen JV and Blagoev B 2011 system-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. 4 rs3

    PubMed  Google Scholar 

  • Ritz-Gold C, Cooke R, Blumenthal D and Stull J 1980 Light chain phosphorylation alters the conformation of skeletal muscle myosin. Biochem. Biophys. Res. Commun. 93 209–214

    CAS  PubMed  Google Scholar 

  • Roach PJ 1991 Multiple and hierarchal protein phosphorylation. J. Biol. Chem. 266 14139–14142

    CAS  PubMed  Google Scholar 

  • Sakamoto N, Iwahana M, Tanaka NG and Osada Y 1991 Inhibition of angiogenesis and tumor growth by synthetic laminin peptide, CDPYIGSR-NH2. Cancer Res. 51 903–906

    CAS  PubMed  Google Scholar 

  • Sarfati G, Dvir T, Elkabets M, Apte RN and Cohen S 2011 Targeting of polymeric nanoparticles to lung metastases by surface-attachment of YIGSR peptide from laminin. Biomaterials 32 152–161

    CAS  PubMed  Google Scholar 

  • Sariahmetoglu M, Crawford BD, Leon H, Sawicka J, Li L, Ballermann BJ, Holmes C, Berthiaume LG, Holt A, Sawicki G and Schulz R 2007 Regulation of matrix metalloproteinase-2 (MMP-2) activity by phosphorylation. FASEB J. 21 2486–2495

    CAS  PubMed  Google Scholar 

  • Sasaki M, Kato S, Kohno K, Martin G and Yamada Y 1987 Sequence of the cDNA encoding the laminin B1 chain reveals a multidomain protein containing cysteine-rich repeats. Proc. Natl. Acad. Sci. USA 84 935–939

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sasaki M, Kleinman H, Huber H, Deutzmann R and Yamada Y 1988 Laminin, a multidomain protein. The A chain has a unique globular domain and homology with the basement membrane proteoglycan and the laminin B chains. J. Biol. Chem. 263 16536–16544

    CAS  PubMed  Google Scholar 

  • Seger D, Gechtman Z and Shaltiel S 1998 Phosphorylation of vitronectin by casein kinase II. Identification of the sites and their promotion of cell adhesion and spreading. J. Biol. Chem. 273 24805–24813

    CAS  PubMed  Google Scholar 

  • Silverberg M, Cho J, Rioux J, McGovern D, Wu J, Annese V, Achkar J, Goyette P, et al. 2009 Ulcerative colitis–risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study. Nat. Genet. 41 216–220

    CAS  PubMed  PubMed Central  Google Scholar 

  • Smyth N, Vatansever HS, Murray P, Meyer M, Frie C, Paulsson M and Edgar D 1999 Absence of basement membranes after targeting the LAMC1 gene results in embryonic lethality due to failure of endoderm differentiation. J. Cell Biol. 144 151–160

    CAS  PubMed  PubMed Central  Google Scholar 

  • Soba P, Eggert S, Wagner K, Zentgraf H, Siehl K, Kreger S, Löwer A, Langer A, Merdes G, Paro R, Masters CL, Müller U, Kins S and Beyreuther K 2005 Homo- and heterodimerization of APP family members promotes intercellular adhesion. EMBO J. 24 3624–3634

    CAS  PubMed  PubMed Central  Google Scholar 

  • Soto C, Estrada L and Castilla J 2006 Amyloids, prions and the inherent infectious nature of misfolded protein aggregates. Trends Biochem. Sci. 31 150–155

    CAS  PubMed  Google Scholar 

  • Stallmach A, Orzechowski HD, Feldmann P, Riecken EO, Zeitz M and Herbst H 1999 32/67-kD laminin receptor expression in human colonic neoplasia: elevated transcript levels correlate with the degree of epithelial dysplasia. Am. J. Gastroenterol. 94 3341–3347

    CAS  PubMed  Google Scholar 

  • Streuli CH, Schmidhauser C, Bailey N, Yurchenco P, Skubitz APN, Roskelley C and Bissell MJ 1995 Laminin mediates tissue-specific gene expression in mammary epithelia. J. Cell Biol. 129 591–603

    CAS  PubMed  Google Scholar 

  • Stuart S, Houel S, Lee T, Wang N, Old W and Ahn N 2015 A Phosphoproteomic Comparison of B-RAFV600E and MKK1/2 inhibitors in melanoma cells. Mol. Cell. Proteomics 14 1599–1615

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sutherland EW Jr and Wosilait WD 1955 Inactivation and activation of liver phosphorylase. Nature 175 169–171

    CAS  PubMed  Google Scholar 

  • Suzuki T, Ando K, Isohara T, Oishi M, Lim GS, Satoh Y, Wasco W, Tanzi RE, Nairn AC, Greengard P, Gandy SE and Kirino Y 1997 Phosphorylation of Alzheimer beta-amyloid precursor-like proteins. Biochemistry 36 4643–4649

    CAS  PubMed  Google Scholar 

  • Tessier-Lavigne M and Goodman CS 1996 The molecular biology of axon guidance. Science 274 1123–1133

    CAS  PubMed  Google Scholar 

  • The UniProt Consortium 2017 UniProt: the universal protein knowledgebase. Nucleic Acids Res. 32 D158–D169. http://uniprot.org

  • Timpl R and Brown J 1996 Supramolecular assembly of basement membranes. BioEssays 18 123–132

    CAS  PubMed  Google Scholar 

  • Timpl R, Rohde H, Robey PG, Rennard SI, Foidart JM and Martin GR 1979 Laminin—a glycoprotein from basement membranes. J. Biol. Chem. 254 9933–9937

    CAS  PubMed  Google Scholar 

  • Trachana V, Christophorides E, Kouzi-Koliakos K and Koliakos G 2005 Laminin-1 is phosphorylated by ecto-protein kinases of monocytes. Int. J. Biochem. Cell Biol. 37 478–492

    CAS  PubMed  Google Scholar 

  • Tsai CF, Wang Y, Yen H, Tsou C, Ku W, Lin P, Chen H, Nesvizhskii A, Ishihama Y and Chen Y 2015 Large-scale determination of absolute phosphorylation stoichiometries in human cells by motif-targeting quantitative proteomics. Nat. Commun. 6 6622

    CAS  PubMed  Google Scholar 

  • Ukawala M, Chaudhari K, Rajyaguru T, Manjappa AS, Murthy RS and Gude R 2012 Laminin receptor-targeted etoposide loaded polymeric micelles: a novel approach for the effective treatment of tumor metastasis. J. Drug Target. 20 55–66

    PubMed  Google Scholar 

  • Underwood P, Bennett F, Kirkpatrick A, Bean P and Moss B 1995 Evidence for the location of a binding sequence for the α2β1 integrin of endothelial cells, in the β1 subunit of laminin. Biochem. J. 309 765–771

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang H, Li M, Lin W, Wang W, Zhang Z, Rayburn ER, Lu J, Chen D, Yue X, Shen F, Jiang F, He J, Wei W, Zeng X and Zhang R 2007 Extracellular activity of cyclic AMP-dependent protein kinase as a biomarker for human cancer detection: distribution characteristics in a normal population and cancer patients. Cancer Epidemiol. Biomarkers Prev. 16 789–795

    CAS  PubMed  Google Scholar 

  • Wu Y, Wang XF, Mo XA, Li JM, Yuan J, Zheng JO, Feng Y and Tang M 2001 Expression of laminin β1 and integrin α2 in the anterior temporal neocortex tissue of patients with intractable epilepsy. Int. J. Neurosci. 121 323–328

    Google Scholar 

  • Yalak G and Vogel V 2014 Ectokinases as novel cancer markers and drug targets in cancer therapy. Cancer Med. 4 404–414

    PubMed  PubMed Central  Google Scholar 

  • Yamamura K, Kibbey MC, Jun SH and Kleinman HK 1993 Effect of Matrigel and laminin peptide YIGSR on tumor growth and metastasis. Semin. Cancer Biol. 4 259–265

    CAS  PubMed  Google Scholar 

  • Yu HN, Zhang LC, Yang JG, Das UN and Shen SR 2009 Effect of laminin tyrosine-isoleucine-glycine-serine-arginine peptide on the growth of human prostate cancer (PC-3) cells in vitro. Eur. J. Pharmacol. 616 251–255

    CAS  PubMed  Google Scholar 

  • Yurchenco PD, Cheng YS and Colognato H 1992 Laminin forms an independent network in basement membranes. J. Cell Biol. 117 1119–1133

    CAS  PubMed  Google Scholar 

  • Zerbino D, Achuthan P, Akanni W, Amode M, Barrell D, Bhai J, Billis K, Cummins C, et al. 2018 Ensembl 2018. Nucleic Acids Res. 46 D754–D761

    CAS  PubMed  Google Scholar 

  • Zhou J 2010 [dataset] CST Curation Set: 9686; Year: 2010; Biosample/Treatment: cell line, PY2/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: RRXp[ST] Antibodies Used to Purify Peptides prior to LCMS: Phospho-PKA Substrate (RRXS/T) (100G7) Rabbit mAb Cat#: 9624, PTMScan(R) Phospho-PKA Substrate Motif (K/RK/RXS*/T*) Immunoaffinity Beads Cat#: 1984

  • Zhou J 2011 [dataset] CST Curation Set: 12497; 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: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991

  • Zimina EP, Fritsch A, Schermer B, Bakulina AY, Bashkurov M, Benzing T and Bruckner-Tuderman L 2007. Extracellular phosphorylation of collagen XVII by ecto-casein kinase 2 inhibits ectodomain shedding. J. Biol. Chem. 282 22737–22746

    CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Papavramidis Theodosis for his assistance and constructive advice in preparing figure 2.

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Correspondence to Georgios Koliakos.

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Communicated by Kundan Sengupta.

Corresponding editor: K undan S engupta

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Verrou, KM., Galliou, P.A., Papaioannou, M. et al. Phosphorylation mapping of Laminin β1-chain: Kinases in association with active sites. J Biosci 44, 55 (2019). https://doi.org/10.1007/s12038-019-9871-9

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