The phosphorylation of the two‐chain form of vitronectin by protein kinase A is heparin dependent

Chain, Daniel G.; Korc‐Grodzicki, Beatriz; Kreizman, Tamar; Shaltiel, Shmuel

doi:10.1016/0014-5793(90)81159-l

Cited by 30 publications

(13 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3a). The 65 kDa form of vitronectin is normally generated by proteolytic processing of the Arg379-Ala380 bond in the C-terminal region of the vitronectin (Chain et al, 1991). The resulting disulfide-linked, two-chain (65 and 10 kDa) isoform of vitronectin is a conformationally distinct form of the glycoprotein that has been shown to preferentially bind heparin (Sane et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

Yersinia pestis uses the Ail outer membrane protein to recruit vitronectin

et al. 2015

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Yersinia pestis uses the Ail outer membrane protein to recruit vitronectin

et al. 2015

View full text Add to dashboard Cite

“…Cleavage in MMP-25 may alter the ability of this protein to bind to clusterin (14). Cleavage in vitronectin abolishes phosphorylation of serine 378 by protein kinase A (27). Although the biologic consequences of these processing events have not been determined in vivo, their occurrence implies physiologic relevance and suggests that similar processing within lubricin will be biologically important.…”

Section: Figmentioning

confidence: 99%

Consequences of Disease-causing Mutations on Lubricin Protein Synthesis, Secretion, and Post-translational Processing

Rhee

Marcelino

Al‐Mayouf

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

Lubricin, a protein product of the gene PRG4, is a secreted mucin-like proteoglycan that is a major lubricant in articulating joints. Mutations in PRG4 cause the autosomal recessive, human disorder camptodactyly-arthropathy-coxa vara-pericarditis syndrome. We developed rabbit polyclonal antibodies against human lubricin to determine the consequence of disease-causing mutations at the protein level and to study the protein's normal post-translational processing. Antiserum generated against an epitope in the amino-terminal portion of lubricin detected protein in wild-type synovial fluid and in conditioned media from wild-type cultured synoviocytes. However, the antiserum did not detect lubricin in synovial fluid or cultured synoviocytes from several patients with frameshift or nonsense mutations in PRG4. Antiserum generated against an epitope in the protein's carboxyl-terminal, hemopexin-like domain identified a post-translational cleavage event in wild-type lubricin, mediated by a subtilisin-like proprotein convertase (SPC). Interestingly, in contrast to wild-type lubricin, one disease-causing mutation that removes the last 8 amino acids of the protein, including a conserved cysteine residue, was not cleaved within the hemopexinlike domain when expressed in COS-7 cells. This suggests that formation of an intrachain disulfide bond is required for SPC-mediated cleavage and that SPC-mediated cleavage is essential to protein function.

show abstract

“…Therefore, rPEDF and plPEDF were incubated with the pure catalytic subunit of PKA and [␥ 32 P]-ATP in the presence of heparin, which stimulates PKA phosphorylation of several substrates. 29 Both rPEDF and plPEDF were equally phosphorylated by PKA in the presence of heparin ( Figure 2C) in a PKI-inhibited manner (not shown), indicating that both proteins contain only a small amount of phosphate incorporated to the PKA site.…”

Section: Ck2 and Pka Phosphorylate Pedf In Vitromentioning

confidence: 99%

Extracellular phosphorylation converts pigment epithelium–derived factor from a neurotrophic to an antiangiogenic factor

Maik-Rachline

Shaltiel

Seger

2005

Blood

Self Cite

View full text Add to dashboard Cite

The pigment epithelium-derived factor (PEDF) belongs to the superfamily of serine protease inhibitors (serpin). There have been 2 distinct functions attributed to this factor, which can act either as a neurotrophic or as an antiangiogenic factor. Besides its localization in the eye, PEDF was recently reported to be present also in human plasma. We found that PEDF purified from plasma is a phosphoprotein, which is extracellularly phosphorylated by protein kinase CK2 (CK2) and to a lesser degree, intracellularly, by protein kinase A (PKA). CK2 phosphorylates PEDF on 2 main residues, Ser24 and Ser114, and PKA phosphorylates PEDF on one residue only, Ser227. The physiologic relevance of these phosphorylations was determined using phosphorylation site mutants. We found that both CK2 and PKA phosphorylations of PEDF markedly affect its physiologic function. The fully CK2 phosphorylation site mutant S24, 114E abolished PEDF neurotrophic activity but enhanced its antiangiogenic activity, while the PKA phosphorylation site mutant S227E reduced PEDF antiangiogenic activity. This is a novel role of extracellular phosphorylation that is shown here to completely change the nature of PEDF from a neutrophic to an antiangiogenic factor. (Blood. 2005;105: 670-678)

show abstract

The phosphorylation of the two‐chain form of vitronectin by protein kinase A is heparin dependent

Cited by 30 publications

References 25 publications

Yersinia pestis uses the Ail outer membrane protein to recruit vitronectin

Yersinia pestis uses the Ail outer membrane protein to recruit vitronectin

Consequences of Disease-causing Mutations on Lubricin Protein Synthesis, Secretion, and Post-translational Processing

Extracellular phosphorylation converts pigment epithelium–derived factor from a neurotrophic to an antiangiogenic factor

Contact Info

Product

Resources

About