Linked Life Data

1590371

Source:http://linkedlifedata.com/resource/pubmed/id/1590371

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5 Pt 1
pubmed:dateCreated
1992-6-25
pubmed:abstractText
We have explored a potential autocrine role for parathyroid hormone-related protein (PTHRP) in malignant squamous carcinoma cells (SqCC) and their nonmalignant counterpart, human epidermal keratinocytes (HK). Specific binding of Tyr36 human PTHRP-(1-36)NH2 (125I-[Tyr36]hPTHRP-(1-36)NH2) was identified in 75% of unselected SqCC lines. In contrast, no binding was detected on the mouse keratinocyte line BALB-MK or on five different HK lines. Although each SqCC and keratinocyte line secreted immunoreactive PTHRP into its medium, there was no correlation between PTHRP concentration and number of binding sites. Inhibition of binding by [Tyr36]hPTHRP-(1-36)NH2 yielded half-maximal inhibitory concentration values of approximately 100 nM in all SqCC lines. Affinity cross-linking of SqCC cells revealed 98- and 70-kDa binding proteins with similar affinity (approximately 100 nM). Exposure of fura-2-loaded SqCC cells to PTHRP and PTH resulted in equivalent, dose-dependent transient increases in intracellular calcium [half-maximal effective concentration (EC50) = 0.08 nM]. PTHRP also increased intracellular calcium in HK (EC50 = 0.05 nM). No adenosine 3',5'-cyclic monophosphate (cAMP) response to PTHRP or PTH was elicited in either SqCC or HK, despite brisk isoproterenol responses in both. We conclude that high-capacity low-affinity binding sites for PTHRP are detectable in the majority of SqCC lines but not in HK. These low-affinity binding sites are unlikely to represent receptors. The sensitive intracellular calcium response suggests the additional presence of high-affinity receptors on SqCC as well as on HK. However, the failure of PTHRP or PTH to stimulate cAMP production in otherwise cyclase-competent cells suggests that these are not classical PTH receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0002-9513
pubmed:author
pubmed:issnType
Print
pubmed:volume
262
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
E599-607
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Analysis of PTHRP binding and signal transduction mechanisms in benign and malignant squamous cells.
pubmed:affiliation
Division of Endocrinology, West Haven Veterans Affairs Medical Center 06516.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't