V. Gastrointestinal peptide signaling through tyrosine phosphorylation of focal adhesion proteins.
Gastrointestinal (GI) peptides (also referred to as neuropeptides or regulatory peptides), including the mammalian bombesin-like peptides gastrin and CCK, elicit the synthesis of classic second messengers (e.g., Ca2+, diacylglycerol, and cAMP) and the consequent stimulation of serine/threonine protein kinase cascades. An emerging theme in signal transduction is that these agonists also induce rapid and coordinate tyrosine phosphorylation of a set of focal adhesion proteins, including the nonreceptor tyrosine kinase p125fak and the adaptor proteins p130cas and paxillin. GI peptide-mediated induction of tyrosine phosphorylation of these focal adhesion proteins is critically dependent on the integrity of the actin cytoskeleton and on functional Rho. The purpose of this article is to review recent advances in unraveling this novel tyrosine kinase pathway(s), because it appears to play a fundamental role in the mediation of important biological effects induced by GI peptides, including cell migration and proliferation.
Rozengurt
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Department of Medicine, Division of Digestive Diseases, School of Medicine and Molecular Biology Institute, University of California, Los Angeles, California 90095, USA.
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002455:Cell Division; D002465:Cell Movement; D050719:Crk-Associated Substrate Protein; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004068:Digestive System Physiological Phenomena; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005768:Gastrointestinal Hormones / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins; D050717:Retinoblastoma-Like Protein p130; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
C493841:BCAR1 protein, human; D015815:Cell Adhesion Molecules; D050719:Crk-Associated Substrate Protein; D003598:Cytoskeletal Proteins; D005768:Gastrointestinal Hormones; C496061:PXN protein, human; D051419:Paxillin; D010750:Phosphoproteins; D011506:Proteins; D050717:Retinoblastoma-Like Protein p130; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D019204:GTP-Binding Proteins